Cardiac arrhythmia induced by genetic silencing of ‘funny’ (f) channels is rescued by GIRK4 inactivation

The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the ‘funny’ current ( I f ) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specif...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications Vol. 5; no. 1; p. 4664
Main Authors:	Mesirca, Pietro, Alig, Jacqueline, Torrente, Angelo G., Müller, Jana Christina, Marger, Laurine, Rollin, Anne, Marquilly, Claire, Vincent, Anne, Dubel, Stefan, Bidaud, Isabelle, Fernandez, Anne, Seniuk, Anika, Engeland, Birgit, Singh, Jasmin, Miquerol, Lucile, Ehmke, Heimo, Eschenhagen, Thomas, Nargeot, Joel, Wickman, Kevin, Isbrandt, Dirk, Mangoni, Matteo E.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 21.08.2014 Nature Publishing Group
Subjects:	14/32 14/34 42/41 631/208/2489/144 631/208/2489/201 631/443/592/75/29 9/74 Animals Arrhythmias, Cardiac - drug therapy Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - physiopathology Benzazepines - pharmacology Calcium Signaling - genetics Cardiology and cardiovascular system Disease Models, Animal Female G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism Genetics Heart Rate - drug effects Human health and pathology Humanities and Social Sciences Humans Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism Inactivation Life Sciences Male Mice Mice, Inbred C57BL Mice, Transgenic multidisciplinary Muscle Proteins - genetics Muscle Proteins - metabolism Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Oocytes - physiology Patch-Clamp Techniques Potassium Channels - genetics Potassium Channels - metabolism Pregnancy Science Science (multidisciplinary) Xenopus Gene therapy Arrhythmias Disease genetics
ISSN:	2041-1723, 2041-1723
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Abstract	The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the ‘funny’ current ( I f ) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific I f silencing caused altered [Ca 2+ ] i release and Ca 2+ handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of I f silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in I f -deficient mice without impairing heartbeat regulation. Our study establishes the role of f -channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. The ‘funny’ current ( I f ) is important for the generation and regulation of the heart’s automaticity. Here the authors show that I f silencing through genetic modification of the f -channel component HCN4 causes heart arrhythmia by altering Ca 2+ handling in pacemaker myocytes.
AbstractList	The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the 'funny' current (If ) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca2+ ]i release and Ca2+ handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If -deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the 'funny' current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca(2+)]i release and Ca(2+) handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the "funny" current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca2+]i release and Ca2+ handling in the sinoatrial node, impaired pacemaker activity, and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the ‘funny’ current ( I f ) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific I f silencing caused altered [Ca 2+ ] i release and Ca 2+ handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of I f silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in I f -deficient mice without impairing heartbeat regulation. Our study establishes the role of f -channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. The ‘funny’ current ( I f ) is important for the generation and regulation of the heart’s automaticity. Here the authors show that I f silencing through genetic modification of the f -channel component HCN4 causes heart arrhythmia by altering Ca 2+ handling in pacemaker myocytes. The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the 'funny' current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca(2+)]i release and Ca(2+) handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases.The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the 'funny' current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca(2+)]i release and Ca(2+) handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases.
ArticleNumber	4664
Author	Bidaud, Isabelle Mesirca, Pietro Torrente, Angelo G. Ehmke, Heimo Isbrandt, Dirk Singh, Jasmin Eschenhagen, Thomas Alig, Jacqueline Mangoni, Matteo E. Dubel, Stefan Müller, Jana Christina Vincent, Anne Fernandez, Anne Engeland, Birgit Rollin, Anne Nargeot, Joel Miquerol, Lucile Wickman, Kevin Seniuk, Anika Marger, Laurine Marquilly, Claire
AuthorAffiliation	3 INSERM U661, Universités de Montpellier 1 & 2, F-34094 Montpellier, France 6 Centre national de la recherche scientifique, UPR-1142, Institut de Génétique Humaine, F-34094, Montpellier, France 11 Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany 9 Université Aix-Marseille, CNRS UMR 7288, Developmental Biology Institute of Marseille, Marseille, France 2 UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, F-34094 Montpellier, France 4 Experimental Neuropediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 8 Department of Experimental Pharmacology and Toxicology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 5 Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Med
AuthorAffiliation_xml	– name: 4 Experimental Neuropediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany – name: 10 Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA – name: 6 Centre national de la recherche scientifique, UPR-1142, Institut de Génétique Humaine, F-34094, Montpellier, France – name: 9 Université Aix-Marseille, CNRS UMR 7288, Developmental Biology Institute of Marseille, Marseille, France – name: 8 Department of Experimental Pharmacology and Toxicology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany – name: 7 Experimental Neurophysiology, University Hospital Cologne, 50937 Cologne, Germany, and German Center for Neurodegenerative Diseases (DZNE), 53175 Bonn, Germany – name: 11 Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany – name: 3 INSERM U661, Universités de Montpellier 1 & 2, F-34094 Montpellier, France – name: 5 Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany – name: 1 Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, F-34094 Montpellier France – name: 2 UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, F-34094 Montpellier, France
Author_xml	– sequence: 1 givenname: Pietro surname: Mesirca fullname: Mesirca, Pietro organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 2 givenname: Jacqueline surname: Alig fullname: Alig, Jacqueline organization: Experimental Neuropediatrics, University Medical Center Hamburg-Eppendorf – sequence: 3 givenname: Angelo G. surname: Torrente fullname: Torrente, Angelo G. organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 4 givenname: Jana Christina surname: Müller fullname: Müller, Jana Christina organization: Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf – sequence: 5 givenname: Laurine surname: Marger fullname: Marger, Laurine organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 6 givenname: Anne surname: Rollin fullname: Rollin, Anne organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 7 givenname: Claire surname: Marquilly fullname: Marquilly, Claire organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 8 givenname: Anne surname: Vincent fullname: Vincent, Anne organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 9 givenname: Stefan surname: Dubel fullname: Dubel, Stefan organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 10 givenname: Isabelle surname: Bidaud fullname: Bidaud, Isabelle organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 11 givenname: Anne surname: Fernandez fullname: Fernandez, Anne organization: Centre national de la recherche scientifique, UPR-1142, Institut de Génétique Humaine – sequence: 12 givenname: Anika surname: Seniuk fullname: Seniuk, Anika organization: Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), University Medical Center Hamburg-Eppendorf – sequence: 13 givenname: Birgit surname: Engeland fullname: Engeland, Birgit organization: Experimental Neuropediatrics, University Medical Center Hamburg-Eppendorf, Experimental Neurophysiology, University Hospital Cologne, German Center for Neurodegenerative Diseases (DZNE) – sequence: 14 givenname: Jasmin surname: Singh fullname: Singh, Jasmin organization: Department of Experimental Pharmacology and Toxicology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf – sequence: 15 givenname: Lucile surname: Miquerol fullname: Miquerol, Lucile organization: Developmental Biology Institute of Marseille, Université Aix-Marseille, CNRS UMR 7288 – sequence: 16 givenname: Heimo surname: Ehmke fullname: Ehmke, Heimo organization: Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), University Medical Center Hamburg-Eppendorf – sequence: 17 givenname: Thomas surname: Eschenhagen fullname: Eschenhagen, Thomas organization: Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), University Medical Center Hamburg-Eppendorf, Department of Experimental Pharmacology and Toxicology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf – sequence: 18 givenname: Joel surname: Nargeot fullname: Nargeot, Joel organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2 – sequence: 19 givenname: Kevin surname: Wickman fullname: Wickman, Kevin organization: Department of Pharmacology, University of Minnesota – sequence: 20 givenname: Dirk surname: Isbrandt fullname: Isbrandt, Dirk organization: Experimental Neuropediatrics, University Medical Center Hamburg-Eppendorf, Experimental Neurophysiology, University Hospital Cologne, German Center for Neurodegenerative Diseases (DZNE) – sequence: 21 givenname: Matteo E. surname: Mangoni fullname: Mangoni, Matteo E. email: matteo.mangoni@igf.cnrs.fr organization: Département de Physiologie, Institut de Génomique Fonctionnelle, LabEx ICST, UMR-5203, Centre national de la recherche scientifique, Universités de Montpellier 1 & 2, INSERM U661, Universités de Montpellier 1 & 2
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/25144323$$D View this record in MEDLINE/PubMed https://hal.science/hal-01059204$$DView record in HAL
BookMark	eNptkstuEzEUhkeoiJbSDQ-ALLFpQQFfZyabSlUEbUUkJARry2MfJ65m7GLPRMqujwGv1yfByZQSAt749v3_OT4-z4sDHzwUxUuC3xHM6vdeh65Loiz5k-KIYk4mpKLsYGd9WJykdIPzYFNSc_6sOKSCcM4oOyramYrGKY1UjMt1v-ycQs6bQYNBzRotwEPvNEquBa-dX6Bg0f3dDzt4v76_-4lO7RnSS-U9tAm5hCIkPYzay-svn3g2U7p3K9W74F8UT61qE5w8zMfFt48fvs6uJvPPl9ezi_lEC077ScNYbRWroKLCMMEs6AoaBlNiSFM2FspagCkVBmwU1HnfKMJsRYnJpLHsuDgffW-HpgOjwfdRtfI2uk7FtQzKyb9vvFvKRVhJTnF2IdngbDRY7smuLuZyc4YJFtNc4dWGPX0IFsP3AVIvO5c0tK3yEIYkiRCipFhsbV_voTdhiD6XYkthTqeiytSr3ewf4__-tAy8GQEdQ0oR7CNCsNw0hfzTFBnGe7B2_fY38std-3_J21GSsq9fQNxJ81_6F1ekzHo
CitedBy_id	crossref_primary_10_3892_ijmm_2017_2877 crossref_primary_10_3389_fphys_2019_01599 crossref_primary_10_1016_j_eplepsyres_2016_08_007 crossref_primary_10_1113_JP285950 crossref_primary_10_1161_CIRCGEN_118_002238 crossref_primary_10_3390_jcdd5010018 crossref_primary_10_1146_annurev_pharmtox_031120_115815 crossref_primary_10_14814_phy2_12561 crossref_primary_10_1016_j_hrthm_2025_02_030 crossref_primary_10_1016_j_disamonth_2023_101637 crossref_primary_10_1007_s00424_022_02698_4 crossref_primary_10_1016_j_bpj_2023_03_024 crossref_primary_10_1007_s00395_018_0701_2 crossref_primary_10_1021_acschemneuro_8b00287 crossref_primary_10_3389_fphys_2020_519382 crossref_primary_10_3389_fcvm_2023_1134503 crossref_primary_10_3390_ijms16011429 crossref_primary_10_1016_j_ceca_2018_12_008 crossref_primary_10_1073_pnas_1517181113 crossref_primary_10_1126_scitranslmed_abc1492 crossref_primary_10_3389_fphys_2021_669029 crossref_primary_10_1038_s41598_017_08191_8 crossref_primary_10_1016_j_biopha_2023_114777 crossref_primary_10_1113_JP270678 crossref_primary_10_1016_j_hrthm_2017_12_027 crossref_primary_10_1038_s41598_018_19719_x crossref_primary_10_1038_s41467_020_19304_9 crossref_primary_10_1080_13685538_2019_1678125 crossref_primary_10_1242_dmm_050101 crossref_primary_10_3389_fgene_2021_654925 crossref_primary_10_1007_s11010_022_04635_6 crossref_primary_10_1016_j_pharmthera_2024_108596 crossref_primary_10_1016_j_hrthm_2024_02_050 crossref_primary_10_1002_admt_202000098 crossref_primary_10_1016_j_pbiomolbio_2021_06_008 crossref_primary_10_3389_fphys_2015_00080 crossref_primary_10_1038_s41598_020_76049_7 crossref_primary_10_3390_cells11071114 crossref_primary_10_1161_CIRCRESAHA_119_316386 crossref_primary_10_1161_CIRCRESAHA_123_323250 crossref_primary_10_1016_j_pbiomolbio_2021_06_003 crossref_primary_10_1124_pr_117_014035 crossref_primary_10_15252_emmm_201606937 crossref_primary_10_1073_pnas_2009393118 crossref_primary_10_1016_j_yjmcc_2015_02_003 crossref_primary_10_1038_s41598_020_66673_8 crossref_primary_10_1113_JP274249 crossref_primary_10_3389_fphys_2024_1386645 crossref_primary_10_3390_jcdd10050194 crossref_primary_10_3389_fphys_2018_00943 crossref_primary_10_1161_CIRCRESAHA_116_310112 crossref_primary_10_1124_molpharm_121_000311 crossref_primary_10_1016_j_pbiomolbio_2021_07_007 crossref_primary_10_1113_JP275303 crossref_primary_10_1038_s41580_018_0052_8 crossref_primary_10_1093_cvr_cvw006 crossref_primary_10_3389_fcvm_2024_1374881 crossref_primary_10_3389_fphys_2022_913506 crossref_primary_10_3390_ijms241310849
Cites_doi	10.1016/j.bpj.2010.06.042 10.1038/6553 10.1073/pnas.0806422106 10.1007/BF02309847 10.1074/jbc.274.18.12835 10.1161/hh0102.102271 10.1073/pnas.0810332106 10.1016/S0076-6879(98)93032-4 10.1161/CIRCRESAHA.109.208041 10.1016/S0092-8674(00)81434-8 10.1016/j.yjmcc.2009.03.022 10.1073/pnas.0935295100 10.1016/j.yjmcc.2011.09.005 10.1085/jgp.20028593 10.1161/CIRCULATIONAHA.107.706887 10.1038/sj.bjp.0703611 10.1093/emboj/cdg032 10.1161/CIRCULATIONAHA.111.075382 10.1016/S0008-6363(00)00153-X 10.1111/j.1540-8167.2010.01905.x 10.1016/S0008-6363(95)00224-3 10.1016/S0896-6273(00)80438-9 10.1093/cvr/cvq390 10.1161/CIRCRESAHA.111.246173 10.1016/j.yjmcc.2008.04.008 10.1073/pnas.89.12.5547 10.1073/pnas.96.16.9391 10.1073/pnas.1010122108 10.1016/j.hrthm.2012.06.026 10.1016/j.cardiores.2004.03.007 10.1161/CIRCULATIONAHA.106.616011 10.1172/JCI6842 10.1016/S0008-6363(01)00370-4 10.1016/S0008-6363(00)00135-8 10.1016/S0008-6363(01)00364-9 10.1007/s00424-003-1127-7 10.1161/CIRCRESAHA.110.220517 10.1146/annurev.ph.55.030193.002323 10.1152/ajpheart.00753.2003 10.1161/CIRCEP.110.949768 10.1172/JCI200316387 10.1161/res.90.1.14 10.1073/pnas.2434235100 10.1146/annurev.physiol.70.113006.100455 10.1073/pnas.1221022110 10.1111/j.1476-5381.1996.tb15505.x 10.1038/31255 10.1161/CIRCRESAHA.107.161778 10.1074/jbc.M311953200 10.1056/NEJM200003093421006 10.1056/NEJMoa052475 10.1113/jphysiol.1986.sp016177 10.4161/chan.5.3.15264 10.1161/01.RES.79.4.691 10.1016/j.cardiores.2006.11.016 10.1038/sj.emboj.7601868 10.1161/CIRCULATIONAHA.113.003712 10.1016/S0009-9236(98)90153-9 10.1152/physrev.00018.2007 10.1146/annurev-physiol-020911-153308 10.1085/jgp.201310996
ContentType	Journal Article
Copyright	Springer Nature Limited 2014 Copyright Nature Publishing Group Aug 2014 Attribution
Copyright_xml	– notice: Springer Nature Limited 2014 – notice: Copyright Nature Publishing Group Aug 2014 – notice: Attribution
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7QL 7QP 7QR 7SN 7SS 7ST 7T5 7T7 7TM 7TO 7X7 7XB 88E 8AO 8FD 8FE 8FG 8FH 8FI 8FJ 8FK ABUWG AEUYN AFKRA ARAPS AZQEC BBNVY BENPR BGLVJ BHPHI C1K CCPQU DWQXO FR3 FYUFA GHDGH GNUQQ H94 HCIFZ K9. LK8 M0S M1P M7P P5Z P62 P64 PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS RC3 SOI 7X8 1XC VOOES 5PM
DOI	10.1038/ncomms5664
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Ecology Abstracts Entomology Abstracts (Full archive) Environment Abstracts Immunology Abstracts Industrial and Applied Microbiology Abstracts (Microbiology A) Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) ProQuest Pharma Collection Technology Research Database ProQuest SciTech Collection ProQuest Technology Collection ProQuest Natural Science Collection ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest One Sustainability ProQuest Central UK/Ireland Advanced Technologies & Computer Science Collection ProQuest Central Essentials Biological Science Collection ProQuest Central Technology Collection Natural Science Collection Environmental Sciences and Pollution Management ProQuest One ProQuest Central Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) ProQuest Biological Science Collection ProQuest Health & Medical Collection Medical Database Biological Science Database ProQuest advanced technologies & aerospace journals ProQuest Advanced Technologies & Aerospace Collection Biotechnology and BioEngineering Abstracts ProQuest Central Premium ProQuest One Academic Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China Genetics Abstracts Environment Abstracts MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest Central Student Oncogenes and Growth Factors Abstracts ProQuest Advanced Technologies & Aerospace Collection ProQuest Central Essentials Nucleic Acids Abstracts SciTech Premium Collection ProQuest Central China Environmental Sciences and Pollution Management ProQuest One Applied & Life Sciences ProQuest One Sustainability Health Research Premium Collection Natural Science Collection Health & Medical Research Collection Biological Science Collection Chemoreception Abstracts Industrial and Applied Microbiology Abstracts (Microbiology A) ProQuest Central (New) ProQuest Medical Library (Alumni) Advanced Technologies & Aerospace Collection ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Hospital Collection ProQuest Technology Collection Health Research Premium Collection (Alumni) Biological Science Database Ecology Abstracts ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts Entomology Abstracts ProQuest Health & Medical Complete ProQuest One Academic UKI Edition Engineering Research Database ProQuest One Academic Calcium & Calcified Tissue Abstracts ProQuest One Academic (New) Technology Collection Technology Research Database ProQuest One Academic Middle East (New) ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central ProQuest Health & Medical Research Collection Genetics Abstracts Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Bacteriology Abstracts (Microbiology B) AIDS and Cancer Research Abstracts ProQuest SciTech Collection Advanced Technologies & Aerospace Database ProQuest Medical Library Immunology Abstracts Environment Abstracts ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	Publicly Available Content Database MEDLINE MEDLINE - Academic
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: PIMPY name: ProQuest Publicly Available Content Database url: http://search.proquest.com/publiccontent sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	2041-1723
EndPage	4664
ExternalDocumentID	PMC4207211 oai:HAL:hal-01059204v1 3409143881 25144323 10_1038_ncomms5664
Genre	Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: NHLBI NIH HHS grantid: R01 HL105550 – fundername: NHLBI NIH HHS grantid: R01 HL087120 – fundername: NHLBI NIH HHS grantid: R01HL087120-A2 – fundername: NHLBI NIH HHS grantid: R01HL105550
GroupedDBID	--- 0R~ 39C 3V. 4.4 53G 70F 7X7 88E 8AO 8FE 8FG 8FH 8FI 8FJ AAHBH AAJSJ ABAWZ ABUWG ACGFO ACGFS ACIWK ACMJI ACPRK ACSMW ADBBV ADFRT ADMLS ADRAZ AENEX AEUYN AFKRA AFRAH AHMBA AJTQC ALIPV ALMA_UNASSIGNED_HOLDINGS AMTXH AOIJS ARAPS ASPBG AVWKF AZFZN BAPOH BBNVY BCNDV BENPR BGLVJ BHPHI BPHCQ BVXVI C6C CCPQU DIK EBLON EBS EE. EJD EMOBN F5P FEDTE FYUFA GROUPED_DOAJ HCIFZ HMCUK HVGLF HYE HZ~ LK8 M1P M48 M7P M~E NAO O9- OK1 P2P P62 PIMPY PQQKQ PROAC PSQYO RNS RNT RNTTT RPM SNYQT SV3 TSG UKHRP AASML AAYXX AFFHD CITATION PHGZM PHGZT PJZUB PPXIY PQGLB CGR CUY CVF ECM EIF NPM 7QL 7QP 7QR 7SN 7SS 7ST 7T5 7T7 7TM 7TO 7XB 8FD 8FK AZQEC C1K DWQXO FR3 GNUQQ H94 K9. P64 PKEHL PQEST PQUKI PRINS RC3 SOI 7X8 PUEGO 1XC 5VS CAG COF KQ8 LGEZI LOTEE NADUK NXXTH VOOES 5PM
ID	FETCH-LOGICAL-c542t-b338fa37e725d353fec7eb3e91d1b6bfe685ed6a0e0dae8fe6ba13f721dec7df3
IEDL.DBID	P5Z
ISICitedReferencesCount	68
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000341057500018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	2041-1723
IngestDate	Tue Nov 04 01:50:27 EST 2025 Tue Oct 14 19:59:42 EDT 2025 Thu Oct 02 05:22:07 EDT 2025 Sat Nov 29 14:43:59 EST 2025 Mon Jul 21 06:00:28 EDT 2025 Sat Nov 29 06:40:32 EST 2025 Tue Nov 18 19:50:40 EST 2025 Fri Feb 21 02:39:49 EST 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	1
Keywords	Gene therapy Arrhythmias Disease genetics
Language	English
License	Attribution: http://creativecommons.org/licenses/by Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c542t-b338fa37e725d353fec7eb3e91d1b6bfe685ed6a0e0dae8fe6ba13f721dec7df3
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-2 content type line 23 PMCID: PMC4207211 Dirk Isbrandt and Matteo E. Mangoni are joint senior authors
ORCID	0000-0002-4743-2068 0000-0003-1721-6564 0000-0002-1812-1447 0000-0002-6094-5247 0000-0002-8892-3373
OpenAccessLink	https://www.proquest.com/docview/1555042957?pq-origsite=%requestingapplication%
PMID	25144323
PQID	1555042957
PQPubID	546298
PageCount	1
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_4207211 hal_primary_oai_HAL_hal_01059204v1 proquest_miscellaneous_1555620511 proquest_journals_1555042957 pubmed_primary_25144323 crossref_primary_10_1038_ncomms5664 crossref_citationtrail_10_1038_ncomms5664 springer_journals_10_1038_ncomms5664
PublicationCentury	2000
PublicationDate	20140821
PublicationDateYYYYMMDD	2014-08-21
PublicationDate_xml	– month: 8 year: 2014 text: 20140821 day: 21
PublicationDecade	2010
PublicationPlace	London
PublicationPlace_xml	– name: London – name: England
PublicationTitle	Nature communications
PublicationTitleAbbrev	Nat Commun
PublicationTitleAlternate	Nat Commun
PublicationYear	2014
Publisher	Nature Publishing Group UK Nature Publishing Group
Publisher_xml	– name: Nature Publishing Group UK – name: Nature Publishing Group
References	Hoesl (CR22) 2008; 45 Vinogradova (CR48) 2010; 107 Verheijck (CR27) 2001; 52 Neco (CR47) 2012; 126 Ishii, Takano, Xie, Noma, Ohmori (CR12) 1999; 274 Ragueneau (CR39) 1998; 64 Seifert (CR13) 1999; 96 Nof (CR17) 2007; 116 Lakatta, DiFrancesco (CR9) 2009; 47 Mangoni, Nargeot (CR1) 2008; 88 CR2 Bertram, Paul, Beyer, Kallfelz (CR4) 1996; 155 Schweizer (CR18) 2010; 3 Ueda (CR20) 2004; 279 Gossen, Bujard (CR24) 1992; 89 Fenske (CR15) 2013; 128 Zhang (CR42) 2008; 102 Vandecasteele (CR64) 1999; 5 Drici, Diochot, Terrenoire, Romey, Lazdunski (CR61) 2000; 131 Alig (CR52) 2009; 106 DiFrancesco, Ferroni, Mazzanti, Tromba (CR30) 1986; 377 Weisbrod (CR43) 2013; 110 Mangrum, DiMarco (CR3) 2000; 342 Liu, Dobrzynski, Yanni, Boyett, Lei (CR28) 2007; 73 Bois, Bescond, Renaudon, Lenfant (CR36) 1996; 118 Bers (CR46) 2008; 70 Bers (CR33) 2002; 90 DiFrancesco (CR7) 1993; 55 Stieber (CR26) 2003; 100 Monfredi, Maltsev, Lakatta (CR38) 2013; 28 Boyett, Honjo, Kodama (CR54) 2000; 47 Joung (CR56) 2011; 22 Kohl, Noble (CR53) 1996; 32 Fenske (CR58) 2011; 109 Herrmann, Fabritz, Layh, Kirchhof, Ludwig (CR41) 2011; 90 Shih, Smith, Toro, Goldin (CR62) 1998; 293 Rigg, Heath, Cui, Terrar (CR49) 2000; 48 Sah (CR35) 1999; 103 Wu (CR51) 2009; 106 Ludwig (CR40) 2003; 22 Gillis (CR6) 2012; 9 Nikmaram, Boyett, Kodama, Suzuki, Honjo (CR55) 1997; 272 Ludwig, Zong, Jeglitsch, Hofmann, Biel (CR10) 1998; 393 DiFrancesco (CR8) 2010; 106 Marger (CR32) 2011; 5 Schulze-Bahr (CR19) 2003; 111 Vinogradova, Bogdanov, Lakatta (CR50) 2002; 90 Clark (CR45) 2004; 286 Yu, Redfern, Fishman (CR25) 1996; 79 Milanesi, Baruscotti, Gnecchi-Ruscone, DiFrancesco (CR16) 2006; 354 Wickman, Nemec, Gendler, Clapham (CR37) 1998; 20 Xie, Sato, Garfinkel, Qu, Weiss (CR57) 2010; 99 Decher, Bundis, Vajna, Steinmeyer (CR63) 2003; 446 Mesirca (CR60) 2013; 142 Santoro (CR11) 1998; 93 Mangoni (CR44) 2003; 100 Mangoni, Nargeot (CR29) 2001; 52 Miquerol (CR31) 2004; 63 Baruscotti (CR23) 2011; 108 Bucchi, Baruscotti, DiFrancesco (CR59) 2002; 120 Bers (CR34) 2014; 76 Dobrzynski, Boyett, Anderson (CR5) 2007; 115 Herrmann, Stieber, Stockl, Hofmann, Ludwig (CR21) 2007; 26 Herrmann, Layh, Ludwig (CR14) 2011; 51 L Miquerol (BFncomms5664_CR31) 2004; 63 L Marger (BFncomms5664_CR32) 2011; 5 M Baruscotti (BFncomms5664_CR23) 2011; 108 TM Ishii (BFncomms5664_CR12) 1999; 274 TM Vinogradova (BFncomms5664_CR48) 2010; 107 H Dobrzynski (BFncomms5664_CR5) 2007; 115 ME Mangoni (BFncomms5664_CR29) 2001; 52 Q Zhang (BFncomms5664_CR42) 2008; 102 S Fenske (BFncomms5664_CR58) 2011; 109 PA Schweizer (BFncomms5664_CR18) 2010; 3 R Seifert (BFncomms5664_CR13) 1999; 96 DM Bers (BFncomms5664_CR33) 2002; 90 P Mesirca (BFncomms5664_CR60) 2013; 142 D DiFrancesco (BFncomms5664_CR7) 1993; 55 O Monfredi (BFncomms5664_CR38) 2013; 28 Y Wu (BFncomms5664_CR51) 2009; 106 A Ludwig (BFncomms5664_CR10) 1998; 393 E Schulze-Bahr (BFncomms5664_CR19) 2003; 111 D Weisbrod (BFncomms5664_CR43) 2013; 110 MR Boyett (BFncomms5664_CR54) 2000; 47 A Ludwig (BFncomms5664_CR40) 2003; 22 M Gossen (BFncomms5664_CR24) 1992; 89 ME Mangoni (BFncomms5664_CR1) 2008; 88 ME Mangoni (BFncomms5664_CR44) 2003; 100 L Rigg (BFncomms5664_CR49) 2000; 48 DM Bers (BFncomms5664_CR46) 2008; 70 P Neco (BFncomms5664_CR47) 2012; 126 J Liu (BFncomms5664_CR28) 2007; 73 D DiFrancesco (BFncomms5664_CR30) 1986; 377 S Herrmann (BFncomms5664_CR14) 2011; 51 A Bucchi (BFncomms5664_CR59) 2002; 120 EE Verheijck (BFncomms5664_CR27) 2001; 52 E Hoesl (BFncomms5664_CR22) 2008; 45 E Nof (BFncomms5664_CR17) 2007; 116 D DiFrancesco (BFncomms5664_CR8) 2010; 106 JM Mangrum (BFncomms5664_CR3) 2000; 342 J Alig (BFncomms5664_CR52) 2009; 106 MD Drici (BFncomms5664_CR61) 2000; 131 S Herrmann (BFncomms5664_CR41) 2011; 90 I Ragueneau (BFncomms5664_CR39) 1998; 64 N Decher (BFncomms5664_CR63) 2003; 446 B Joung (BFncomms5664_CR56) 2011; 22 J Stieber (BFncomms5664_CR26) 2003; 100 K Wickman (BFncomms5664_CR37) 1998; 20 R Milanesi (BFncomms5664_CR16) 2006; 354 TM Shih (BFncomms5664_CR62) 1998; 293 P Kohl (BFncomms5664_CR53) 1996; 32 BFncomms5664_CR2 B Santoro (BFncomms5664_CR11) 1998; 93 H Bertram (BFncomms5664_CR4) 1996; 155 S Fenske (BFncomms5664_CR15) 2013; 128 S Herrmann (BFncomms5664_CR21) 2007; 26 Y Xie (BFncomms5664_CR57) 2010; 99 P Bois (BFncomms5664_CR36) 1996; 118 VP Sah (BFncomms5664_CR35) 1999; 103 DM Bers (BFncomms5664_CR34) 2014; 76 EG Lakatta (BFncomms5664_CR9) 2009; 47 RB Clark (BFncomms5664_CR45) 2004; 286 AM Gillis (BFncomms5664_CR6) 2012; 9 K Ueda (BFncomms5664_CR20) 2004; 279 TM Vinogradova (BFncomms5664_CR50) 2002; 90 MR Nikmaram (BFncomms5664_CR55) 1997; 272 G Vandecasteele (BFncomms5664_CR64) 1999; 5 Z Yu (BFncomms5664_CR25) 1996; 79 12084770 - J Gen Physiol. 2002 Jul;120(1):1-13 17420362 - Circulation. 2007 Apr 10;115(14):1921-32 10430953 - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9391-6 12700358 - Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5543-8 10377168 - J Clin Invest. 1999 Jun;103(12):1627-34 9227558 - Am J Physiol. 1997 Jun;272(6 Pt 2):H2782-92 18626064 - Physiol Rev. 2008 Jul;88(3):919-82 23858001 - J Gen Physiol. 2013 Aug;142(2):113-26 11786521 - Circ Res. 2002 Jan 11;90(1):73-9 19276108 - Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5972-7 9634236 - Nature. 1998 Jun 11;393(6685):587-91 17988210 - Annu Rev Physiol. 2008;70:23-49 21945247 - J Mol Cell Cardiol. 2011 Dec;51(6):997-1006 9630217 - Cell. 1998 May 29;93(5):717-29 11054472 - Cardiovasc Res. 2000 Nov;48(2):254-64 8831492 - Circ Res. 1996 Oct;79(4):691-7 23589888 - Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):E1685-94 9711627 - Methods Enzymol. 1998;293:529-56 15123648 - J Biol Chem. 2004 Jun 25;279(26):27194-8 8750801 - Eur J Pediatr. 1996 Jan;155(1):7-10 12856183 - Pflugers Arch. 2003 Sep;446(6):633-40 12514127 - EMBO J. 2003 Jan 15;22(2):216-24 14693686 - Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1757-66 20816052 - Biophys J. 2010 Sep 8;99(5):1408-15 17222809 - Cardiovasc Res. 2007 Mar 1;73(4):729-38 22858114 - Heart Rhythm. 2012 Aug;9(8):1344-65 20693575 - Circ Arrhythm Electrophysiol. 2010 Oct;3(5):542-52 21193513 - Cardiovasc Res. 2011 Apr 1;90(1):38-48 1319065 - Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51 24245942 - Annu Rev Physiol. 2014;76:107-27 17914461 - EMBO J. 2007 Oct 31;26(21):4423-32 21406959 - Channels (Austin). 2011 May-Jun;5(3):241-50 22711277 - Circulation. 2012 Jul 24;126(4):392-401 14657344 - Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15235-40 8799581 - Br J Pharmacol. 1996 Jun;118(4):1051-7 10212270 - J Biol Chem. 1999 Apr 30;274(18):12835-9 23455768 - Physiology (Bethesda). 2013 Mar;28(2):74-92 15194464 - Cardiovasc Res. 2004 Jul 1;63(1):77-86 21040091 - J Cardiovasc Electrophysiol. 2011 Apr;22(4):448-54 18538341 - J Mol Cell Cardiol. 2008 Jul;45(1):62-9 17646576 - Circulation. 2007 Jul 31;116(5):463-70 24218458 - Circulation. 2013 Dec 17;128(24):2585-94 19570998 - Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12189-94 11786512 - Circ Res. 2002 Jan 11;90(1):14-7 19361514 - J Mol Cell Cardiol. 2009 Aug;47(2):157-70 11015309 - Br J Pharmacol. 2000 Oct;131(3):569-77 2432247 - J Physiol. 1986 Aug;377:61-88 8776404 - Cardiovasc Res. 1996 Jul;32(1):62-8 16407510 - N Engl J Med. 2006 Jan 12;354(2):151-7 12750403 - J Clin Invest. 2003 May;111(10):1537-45 11557233 - Cardiovasc Res. 2001 Oct;52(1):51-64 9728900 - Clin Pharmacol Ther. 1998 Aug;64(2):192-203 20167941 - Circ Res. 2010 Feb 19;106(3):434-46 9459446 - Neuron. 1998 Jan;20(1):103-14 21903939 - Circ Res. 2011 Oct 14;109(9):1015-23 11557232 - Cardiovasc Res. 2001 Oct;52(1):40-50 10086391 - Nat Med. 1999 Mar;5(3):331-4 10706901 - N Engl J Med. 2000 Mar 9;342(10):703-9 10974216 - Cardiovasc Res. 2000 Sep;47(4):658-87 7682045 - Annu Rev Physiol. 1993;55:455-72 20651285 - Circ Res. 2010 Sep 17;107(6):767-75 18096820 - Circ Res. 2008 Feb 29;102(4):465-71 21220308 - Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1705-10
References_xml	– volume: 99 start-page: 1408 year: 2010 end-page: 1415 ident: CR57 article-title: So little source, so much sink: requirements for afterdepolarizations to propagate in tissue publication-title: Biophys. J. doi: 10.1016/j.bpj.2010.06.042 – volume: 5 start-page: 331 year: 1999 end-page: 334 ident: CR64 article-title: Muscarinic and beta-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase publication-title: Nat. Med. doi: 10.1038/6553 – volume: 106 start-page: 5972 year: 2009 end-page: 5977 ident: CR51 article-title: Calmodulin kinase II is required for fight or flight sinoatrial node physiology publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0806422106 – volume: 155 start-page: 7 year: 1996 end-page: 10 ident: CR4 article-title: Familial idiopathic atrial fibrillation with bradyarrhythmia publication-title: Eur. J. Pediatr. doi: 10.1007/BF02309847 – volume: 274 start-page: 12835 year: 1999 end-page: 12839 ident: CR12 article-title: Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.18.12835 – volume: 90 start-page: 73 year: 2002 end-page: 79 ident: CR50 article-title: beta-Adrenergic stimulation modulates ryanodine receptor Ca2+ release during diastolic depolarization to accelerate pacemaker activity in rabbit sinoatrial nodal cells publication-title: Circ. Res. doi: 10.1161/hh0102.102271 – volume: 106 start-page: 12189 year: 2009 end-page: 12194 ident: CR52 article-title: Control of heart rate by cAMP sensitivity of HCN channels publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0810332106 – volume: 293 start-page: 529 year: 1998 end-page: 556 ident: CR62 article-title: High-level expression and detection of ion channels in oocytes publication-title: Methods Enzymol. doi: 10.1016/S0076-6879(98)93032-4 – volume: 106 start-page: 434 year: 2010 end-page: 446 ident: CR8 article-title: The role of the funny current in pacemaker activity publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.109.208041 – volume: 93 start-page: 717 year: 1998 end-page: 729 ident: CR11 article-title: Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain publication-title: Cell doi: 10.1016/S0092-8674(00)81434-8 – volume: 47 start-page: 157 year: 2009 end-page: 170 ident: CR9 article-title: What keeps us ticking: a funny current, a calcium clock, or both? publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2009.03.022 – volume: 100 start-page: 5543 year: 2003 end-page: 5548 ident: CR44 article-title: Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0935295100 – volume: 51 start-page: 997 year: 2011 end-page: 1006 ident: CR14 article-title: Novel insights into the distribution of cardiac HCN channels: An expression study in the mouse heart publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2011.09.005 – volume: 120 start-page: 1 year: 2002 end-page: 13 ident: CR59 article-title: Current-dependent block of rabbit sino-atrial node If channels by ivabradine publication-title: J. Gen. Physiol. doi: 10.1085/jgp.20028593 – volume: 116 start-page: 463 year: 2007 end-page: 470 ident: CR17 article-title: Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.107.706887 – volume: 131 start-page: 569 year: 2000 end-page: 577 ident: CR61 article-title: The bee venom peptide tertiapin underlines the role of IKACh in acetylcholine-induced atrioventricular blocks publication-title: Br. J. Pharmacol. doi: 10.1038/sj.bjp.0703611 – volume: 22 start-page: 216 year: 2003 end-page: 224 ident: CR40 article-title: Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2 publication-title: EMBO J. doi: 10.1093/emboj/cdg032 – volume: 126 start-page: 392 year: 2012 end-page: 401 ident: CR47 article-title: Paradoxical effect of increased diastolic Ca2+ release and decreased sinoatrial node activity in a mouse model of catecholaminergic polymorphic ventricular tachycardia publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.111.075382 – volume: 48 start-page: 254 year: 2000 end-page: 264 ident: CR49 article-title: Localisation and functional significance of ryanodine receptors during beta-adrenoceptor stimulation in the guinea-pig sino-atrial node publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(00)00153-X – volume: 22 start-page: 448 year: 2011 end-page: 454 ident: CR56 article-title: Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia publication-title: J. Cardiovasc. Electrophysiol. doi: 10.1111/j.1540-8167.2010.01905.x – volume: 32 start-page: 62 year: 1996 end-page: 68 ident: CR53 article-title: Mechanosensitive connective tissue: potential influence on heart rhythm publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(95)00224-3 – volume: 20 start-page: 103 year: 1998 end-page: 114 ident: CR37 article-title: Abnormal heart rate regulation in GIRK4 knockout mice publication-title: Neuron doi: 10.1016/S0896-6273(00)80438-9 – volume: 90 start-page: 38 year: 2011 end-page: 48 ident: CR41 article-title: Insights into sick sinus syndrome from an inducible mouse model publication-title: Cardiovasc. Res. doi: 10.1093/cvr/cvq390 – volume: 109 start-page: 1015 year: 2011 end-page: 1023 ident: CR58 article-title: HCN3 contributes to the ventricular action potential waveform in the murine heart publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.111.246173 – volume: 45 start-page: 62 year: 2008 end-page: 69 ident: CR22 article-title: Tamoxifen-inducible gene deletion in the cardiac conduction system publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2008.04.008 – volume: 89 start-page: 5547 year: 1992 end-page: 5551 ident: CR24 article-title: Tight control of gene expression in mammalian cells by tetracycline-responsive promoters publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.89.12.5547 – volume: 96 start-page: 9391 year: 1999 end-page: 9396 ident: CR13 article-title: Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.96.16.9391 – volume: 108 start-page: 1705 year: 2011 end-page: 1710 ident: CR23 article-title: Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1010122108 – volume: 9 start-page: 1344 year: 2012 end-page: 1365 ident: CR6 article-title: HRS/ACCF expert consensus statement on pacemaker device and mode selection. Developed in partnership between the Heart Rhythm Society (HRS) and the American College of Cardiology Foundation (ACCF) and in collaboration with the Society of Thoracic Surgeons publication-title: Heart Rhythm doi: 10.1016/j.hrthm.2012.06.026 – volume: 63 start-page: 77 year: 2004 end-page: 86 ident: CR31 article-title: Architectural and functional asymmetry of the His-Purkinje system of the murine heart publication-title: Cardiovasc. Res. doi: 10.1016/j.cardiores.2004.03.007 – volume: 115 start-page: 1921 year: 2007 end-page: 1932 ident: CR5 article-title: New insights into pacemaker activity: promoting understanding of sick sinus syndrome publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.106.616011 – volume: 28 start-page: 74 year: 2013 end-page: 92 ident: CR38 article-title: Modern concepts concerning the origin of the heartbeat publication-title: Physiology (Bethesda) – volume: 103 start-page: 1627 year: 1999 end-page: 1634 ident: CR35 article-title: Cardiac-specific overexpression of RhoA results in sinus and atrioventricular nodal dysfunction and contractile failure publication-title: J. Clin. Invest. doi: 10.1172/JCI6842 – volume: 52 start-page: 51 year: 2001 end-page: 64 ident: CR29 article-title: Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(01)00370-4 – volume: 47 start-page: 658 year: 2000 end-page: 687 ident: CR54 article-title: The sinoatrial node, a heterogeneous pacemaker structure publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(00)00135-8 – volume: 52 start-page: 40 year: 2001 end-page: 50 ident: CR27 article-title: Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(01)00364-9 – volume: 446 start-page: 633 year: 2003 end-page: 640 ident: CR63 article-title: KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents publication-title: Pflugers Arch. doi: 10.1007/s00424-003-1127-7 – volume: 107 start-page: 767 year: 2010 end-page: 775 ident: CR48 article-title: Sarcoplasmic reticulum Ca2+ pumping kinetics regulates timing of local Ca2+ releases and spontaneous beating rate of rabbit sinoatrial node pacemaker cells publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.110.220517 – volume: 55 start-page: 455 year: 1993 end-page: 472 ident: CR7 article-title: Pacemaker mechanisms in cardiac tissue publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev.ph.55.030193.002323 – volume: 286 start-page: H1757 year: 2004 end-page: H1766 ident: CR45 article-title: A rapidly activating delayed rectifier K+ current regulates pacemaker activity in adult mouse sinoatrial node cells publication-title: Am. J. Physiol. Heart Circ. Physiol. doi: 10.1152/ajpheart.00753.2003 – volume: 3 start-page: 542 year: 2010 end-page: 552 ident: CR18 article-title: cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control publication-title: Circ. Arrhythm. Electrophysiol. doi: 10.1161/CIRCEP.110.949768 – volume: 111 start-page: 1537 year: 2003 end-page: 1545 ident: CR19 article-title: Pacemaker channel dysfunction in a patient with sinus node disease publication-title: J. Clin. Invest. doi: 10.1172/JCI200316387 – ident: CR2 – volume: 90 start-page: 14 year: 2002 end-page: 17 ident: CR33 article-title: Calcium and cardiac rhythms: physiological and pathophysiological publication-title: Circ. Res. doi: 10.1161/res.90.1.14 – volume: 100 start-page: 15235 year: 2003 end-page: 15240 ident: CR26 article-title: The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.2434235100 – volume: 70 start-page: 23 year: 2008 end-page: 49 ident: CR46 article-title: Calcium cycling and signaling in cardiac myocytes publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev.physiol.70.113006.100455 – volume: 110 start-page: E1685 year: 2013 end-page: E1694 ident: CR43 article-title: SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1221022110 – volume: 118 start-page: 1051 year: 1996 end-page: 1057 ident: CR36 article-title: Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells publication-title: Br. J. Pharmacol. doi: 10.1111/j.1476-5381.1996.tb15505.x – volume: 393 start-page: 587 year: 1998 end-page: 591 ident: CR10 article-title: A family of hyperpolarization-activated mammalian cation channels publication-title: Nature doi: 10.1038/31255 – volume: 102 start-page: 465 year: 2008 end-page: 471 ident: CR42 article-title: Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.107.161778 – volume: 279 start-page: 27194 year: 2004 end-page: 27198 ident: CR20 article-title: Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia publication-title: J. Biol. Chem. doi: 10.1074/jbc.M311953200 – volume: 342 start-page: 703 year: 2000 end-page: 709 ident: CR3 article-title: The evaluation and management of bradycardia publication-title: N. Engl. J. Med. doi: 10.1056/NEJM200003093421006 – volume: 354 start-page: 151 year: 2006 end-page: 157 ident: CR16 article-title: Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa052475 – volume: 377 start-page: 61 year: 1986 end-page: 88 ident: CR30 article-title: Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node publication-title: J. Physiol. doi: 10.1113/jphysiol.1986.sp016177 – volume: 5 start-page: 241 year: 2011 end-page: 250 ident: CR32 article-title: Pacemaker activity and ionic currents in mouse atrioventricular node cells publication-title: Channels (Austin) doi: 10.4161/chan.5.3.15264 – volume: 272 start-page: H2782 year: 1997 end-page: H2792 ident: CR55 article-title: Variation in effects of Cs+, UL-FS-49, and ZD-7288 within sinoatrial node publication-title: Am. J. Physiol. – volume: 79 start-page: 691 year: 1996 end-page: 697 ident: CR25 article-title: Conditional transgene expression in the heart publication-title: Circ. Res. doi: 10.1161/01.RES.79.4.691 – volume: 73 start-page: 729 year: 2007 end-page: 738 ident: CR28 article-title: Organisation of the mouse sinoatrial node: structure and expression of HCN channels publication-title: Cardiovasc. Res. doi: 10.1016/j.cardiores.2006.11.016 – volume: 26 start-page: 4423 year: 2007 end-page: 4432 ident: CR21 article-title: HCN4 provides a ‘depolarization reserve’ and is not required for heart rate acceleration in mice publication-title: EMBO J. doi: 10.1038/sj.emboj.7601868 – volume: 128 start-page: 2585 year: 2013 end-page: 2594 ident: CR15 article-title: Sick sinus syndrome in HCN1-deficient mice publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.113.003712 – volume: 64 start-page: 192 year: 1998 end-page: 203 ident: CR39 article-title: Pharmacokinetic-pharmacodynamic modeling of the effects of ivabradine, a direct sinus node inhibitor, on heart rate in healthy volunteers publication-title: Clin. Pharmacol. Ther. doi: 10.1016/S0009-9236(98)90153-9 – volume: 88 start-page: 919 year: 2008 end-page: 982 ident: CR1 article-title: Genesis and regulation of the heart automaticity publication-title: Physiol. Rev. doi: 10.1152/physrev.00018.2007 – volume: 76 start-page: 107 year: 2014 end-page: 127 ident: CR34 article-title: Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev-physiol-020911-153308 – volume: 142 start-page: 113 year: 2013 end-page: 126 ident: CR60 article-title: The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation publication-title: J. Gen. Physiol. doi: 10.1085/jgp.201310996 – volume: 115 start-page: 1921 year: 2007 ident: BFncomms5664_CR5 publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.106.616011 – volume: 342 start-page: 703 year: 2000 ident: BFncomms5664_CR3 publication-title: N. Engl. J. Med. doi: 10.1056/NEJM200003093421006 – volume: 63 start-page: 77 year: 2004 ident: BFncomms5664_CR31 publication-title: Cardiovasc. Res. doi: 10.1016/j.cardiores.2004.03.007 – volume: 354 start-page: 151 year: 2006 ident: BFncomms5664_CR16 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa052475 – volume: 100 start-page: 15235 year: 2003 ident: BFncomms5664_CR26 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.2434235100 – volume: 52 start-page: 51 year: 2001 ident: BFncomms5664_CR29 publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(01)00370-4 – volume: 118 start-page: 1051 year: 1996 ident: BFncomms5664_CR36 publication-title: Br. J. Pharmacol. doi: 10.1111/j.1476-5381.1996.tb15505.x – volume: 48 start-page: 254 year: 2000 ident: BFncomms5664_CR49 publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(00)00153-X – volume: 106 start-page: 5972 year: 2009 ident: BFncomms5664_CR51 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0806422106 – volume: 272 start-page: H2782 year: 1997 ident: BFncomms5664_CR55 publication-title: Am. J. Physiol. – volume: 155 start-page: 7 year: 1996 ident: BFncomms5664_CR4 publication-title: Eur. J. Pediatr. doi: 10.1007/BF02309847 – volume: 96 start-page: 9391 year: 1999 ident: BFncomms5664_CR13 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.96.16.9391 – volume: 116 start-page: 463 year: 2007 ident: BFncomms5664_CR17 publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.107.706887 – volume: 26 start-page: 4423 year: 2007 ident: BFncomms5664_CR21 publication-title: EMBO J. doi: 10.1038/sj.emboj.7601868 – volume: 293 start-page: 529 year: 1998 ident: BFncomms5664_CR62 publication-title: Methods Enzymol. doi: 10.1016/S0076-6879(98)93032-4 – volume: 73 start-page: 729 year: 2007 ident: BFncomms5664_CR28 publication-title: Cardiovasc. Res. doi: 10.1016/j.cardiores.2006.11.016 – volume: 22 start-page: 216 year: 2003 ident: BFncomms5664_CR40 publication-title: EMBO J. doi: 10.1093/emboj/cdg032 – volume: 99 start-page: 1408 year: 2010 ident: BFncomms5664_CR57 publication-title: Biophys. J. doi: 10.1016/j.bpj.2010.06.042 – volume: 142 start-page: 113 year: 2013 ident: BFncomms5664_CR60 publication-title: J. Gen. Physiol. doi: 10.1085/jgp.201310996 – volume: 89 start-page: 5547 year: 1992 ident: BFncomms5664_CR24 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.89.12.5547 – volume: 110 start-page: E1685 year: 2013 ident: BFncomms5664_CR43 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1221022110 – volume: 47 start-page: 658 year: 2000 ident: BFncomms5664_CR54 publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(00)00135-8 – ident: BFncomms5664_CR2 – volume: 28 start-page: 74 year: 2013 ident: BFncomms5664_CR38 publication-title: Physiology (Bethesda) – volume: 446 start-page: 633 year: 2003 ident: BFncomms5664_CR63 publication-title: Pflugers Arch. doi: 10.1007/s00424-003-1127-7 – volume: 79 start-page: 691 year: 1996 ident: BFncomms5664_CR25 publication-title: Circ. Res. doi: 10.1161/01.RES.79.4.691 – volume: 126 start-page: 392 year: 2012 ident: BFncomms5664_CR47 publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.111.075382 – volume: 9 start-page: 1344 year: 2012 ident: BFncomms5664_CR6 publication-title: Heart Rhythm doi: 10.1016/j.hrthm.2012.06.026 – volume: 64 start-page: 192 year: 1998 ident: BFncomms5664_CR39 publication-title: Clin. Pharmacol. Ther. doi: 10.1016/S0009-9236(98)90153-9 – volume: 5 start-page: 331 year: 1999 ident: BFncomms5664_CR64 publication-title: Nat. Med. doi: 10.1038/6553 – volume: 279 start-page: 27194 year: 2004 ident: BFncomms5664_CR20 publication-title: J. Biol. Chem. doi: 10.1074/jbc.M311953200 – volume: 286 start-page: H1757 year: 2004 ident: BFncomms5664_CR45 publication-title: Am. J. Physiol. Heart Circ. Physiol. doi: 10.1152/ajpheart.00753.2003 – volume: 90 start-page: 14 year: 2002 ident: BFncomms5664_CR33 publication-title: Circ. Res. doi: 10.1161/res.90.1.14 – volume: 377 start-page: 61 year: 1986 ident: BFncomms5664_CR30 publication-title: J. Physiol. doi: 10.1113/jphysiol.1986.sp016177 – volume: 106 start-page: 12189 year: 2009 ident: BFncomms5664_CR52 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0810332106 – volume: 70 start-page: 23 year: 2008 ident: BFncomms5664_CR46 publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev.physiol.70.113006.100455 – volume: 22 start-page: 448 year: 2011 ident: BFncomms5664_CR56 publication-title: J. Cardiovasc. Electrophysiol. doi: 10.1111/j.1540-8167.2010.01905.x – volume: 32 start-page: 62 year: 1996 ident: BFncomms5664_CR53 publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(95)00224-3 – volume: 52 start-page: 40 year: 2001 ident: BFncomms5664_CR27 publication-title: Cardiovasc. Res. doi: 10.1016/S0008-6363(01)00364-9 – volume: 5 start-page: 241 year: 2011 ident: BFncomms5664_CR32 publication-title: Channels (Austin) doi: 10.4161/chan.5.3.15264 – volume: 109 start-page: 1015 year: 2011 ident: BFncomms5664_CR58 publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.111.246173 – volume: 88 start-page: 919 year: 2008 ident: BFncomms5664_CR1 publication-title: Physiol. Rev. doi: 10.1152/physrev.00018.2007 – volume: 393 start-page: 587 year: 1998 ident: BFncomms5664_CR10 publication-title: Nature doi: 10.1038/31255 – volume: 107 start-page: 767 year: 2010 ident: BFncomms5664_CR48 publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.110.220517 – volume: 108 start-page: 1705 year: 2011 ident: BFncomms5664_CR23 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1010122108 – volume: 76 start-page: 107 year: 2014 ident: BFncomms5664_CR34 publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev-physiol-020911-153308 – volume: 120 start-page: 1 year: 2002 ident: BFncomms5664_CR59 publication-title: J. Gen. Physiol. doi: 10.1085/jgp.20028593 – volume: 20 start-page: 103 year: 1998 ident: BFncomms5664_CR37 publication-title: Neuron doi: 10.1016/S0896-6273(00)80438-9 – volume: 106 start-page: 434 year: 2010 ident: BFncomms5664_CR8 publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.109.208041 – volume: 45 start-page: 62 year: 2008 ident: BFncomms5664_CR22 publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2008.04.008 – volume: 111 start-page: 1537 year: 2003 ident: BFncomms5664_CR19 publication-title: J. Clin. Invest. doi: 10.1172/JCI200316387 – volume: 128 start-page: 2585 year: 2013 ident: BFncomms5664_CR15 publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.113.003712 – volume: 55 start-page: 455 year: 1993 ident: BFncomms5664_CR7 publication-title: Annu. Rev. Physiol. doi: 10.1146/annurev.ph.55.030193.002323 – volume: 93 start-page: 717 year: 1998 ident: BFncomms5664_CR11 publication-title: Cell doi: 10.1016/S0092-8674(00)81434-8 – volume: 90 start-page: 38 year: 2011 ident: BFncomms5664_CR41 publication-title: Cardiovasc. Res. doi: 10.1093/cvr/cvq390 – volume: 3 start-page: 542 year: 2010 ident: BFncomms5664_CR18 publication-title: Circ. Arrhythm. Electrophysiol. doi: 10.1161/CIRCEP.110.949768 – volume: 51 start-page: 997 year: 2011 ident: BFncomms5664_CR14 publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2011.09.005 – volume: 47 start-page: 157 year: 2009 ident: BFncomms5664_CR9 publication-title: J. Mol. Cell Cardiol. doi: 10.1016/j.yjmcc.2009.03.022 – volume: 90 start-page: 73 year: 2002 ident: BFncomms5664_CR50 publication-title: Circ. Res. doi: 10.1161/hh0102.102271 – volume: 274 start-page: 12835 year: 1999 ident: BFncomms5664_CR12 publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.18.12835 – volume: 102 start-page: 465 year: 2008 ident: BFncomms5664_CR42 publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.107.161778 – volume: 100 start-page: 5543 year: 2003 ident: BFncomms5664_CR44 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0935295100 – volume: 103 start-page: 1627 year: 1999 ident: BFncomms5664_CR35 publication-title: J. Clin. Invest. doi: 10.1172/JCI6842 – volume: 131 start-page: 569 year: 2000 ident: BFncomms5664_CR61 publication-title: Br. J. Pharmacol. doi: 10.1038/sj.bjp.0703611 – reference: 19570998 - Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12189-94 – reference: 18626064 - Physiol Rev. 2008 Jul;88(3):919-82 – reference: 12856183 - Pflugers Arch. 2003 Sep;446(6):633-40 – reference: 18096820 - Circ Res. 2008 Feb 29;102(4):465-71 – reference: 9227558 - Am J Physiol. 1997 Jun;272(6 Pt 2):H2782-92 – reference: 12514127 - EMBO J. 2003 Jan 15;22(2):216-24 – reference: 11054472 - Cardiovasc Res. 2000 Nov;48(2):254-64 – reference: 8799581 - Br J Pharmacol. 1996 Jun;118(4):1051-7 – reference: 9634236 - Nature. 1998 Jun 11;393(6685):587-91 – reference: 8776404 - Cardiovasc Res. 1996 Jul;32(1):62-8 – reference: 24245942 - Annu Rev Physiol. 2014;76:107-27 – reference: 11786521 - Circ Res. 2002 Jan 11;90(1):73-9 – reference: 11557233 - Cardiovasc Res. 2001 Oct;52(1):51-64 – reference: 19276108 - Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5972-7 – reference: 11557232 - Cardiovasc Res. 2001 Oct;52(1):40-50 – reference: 23858001 - J Gen Physiol. 2013 Aug;142(2):113-26 – reference: 16407510 - N Engl J Med. 2006 Jan 12;354(2):151-7 – reference: 21406959 - Channels (Austin). 2011 May-Jun;5(3):241-50 – reference: 8750801 - Eur J Pediatr. 1996 Jan;155(1):7-10 – reference: 10974216 - Cardiovasc Res. 2000 Sep;47(4):658-87 – reference: 1319065 - Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51 – reference: 2432247 - J Physiol. 1986 Aug;377:61-88 – reference: 11786512 - Circ Res. 2002 Jan 11;90(1):14-7 – reference: 20693575 - Circ Arrhythm Electrophysiol. 2010 Oct;3(5):542-52 – reference: 9728900 - Clin Pharmacol Ther. 1998 Aug;64(2):192-203 – reference: 11015309 - Br J Pharmacol. 2000 Oct;131(3):569-77 – reference: 21903939 - Circ Res. 2011 Oct 14;109(9):1015-23 – reference: 17988210 - Annu Rev Physiol. 2008;70:23-49 – reference: 20167941 - Circ Res. 2010 Feb 19;106(3):434-46 – reference: 23589888 - Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):E1685-94 – reference: 20651285 - Circ Res. 2010 Sep 17;107(6):767-75 – reference: 15123648 - J Biol Chem. 2004 Jun 25;279(26):27194-8 – reference: 10706901 - N Engl J Med. 2000 Mar 9;342(10):703-9 – reference: 10377168 - J Clin Invest. 1999 Jun;103(12):1627-34 – reference: 18538341 - J Mol Cell Cardiol. 2008 Jul;45(1):62-9 – reference: 14693686 - Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1757-66 – reference: 17914461 - EMBO J. 2007 Oct 31;26(21):4423-32 – reference: 12700358 - Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5543-8 – reference: 9711627 - Methods Enzymol. 1998;293:529-56 – reference: 23455768 - Physiology (Bethesda). 2013 Mar;28(2):74-92 – reference: 14657344 - Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15235-40 – reference: 9459446 - Neuron. 1998 Jan;20(1):103-14 – reference: 9630217 - Cell. 1998 May 29;93(5):717-29 – reference: 17420362 - Circulation. 2007 Apr 10;115(14):1921-32 – reference: 20816052 - Biophys J. 2010 Sep 8;99(5):1408-15 – reference: 12084770 - J Gen Physiol. 2002 Jul;120(1):1-13 – reference: 12750403 - J Clin Invest. 2003 May;111(10):1537-45 – reference: 19361514 - J Mol Cell Cardiol. 2009 Aug;47(2):157-70 – reference: 22711277 - Circulation. 2012 Jul 24;126(4):392-401 – reference: 22858114 - Heart Rhythm. 2012 Aug;9(8):1344-65 – reference: 15194464 - Cardiovasc Res. 2004 Jul 1;63(1):77-86 – reference: 21193513 - Cardiovasc Res. 2011 Apr 1;90(1):38-48 – reference: 10086391 - Nat Med. 1999 Mar;5(3):331-4 – reference: 10430953 - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9391-6 – reference: 7682045 - Annu Rev Physiol. 1993;55:455-72 – reference: 8831492 - Circ Res. 1996 Oct;79(4):691-7 – reference: 10212270 - J Biol Chem. 1999 Apr 30;274(18):12835-9 – reference: 21945247 - J Mol Cell Cardiol. 2011 Dec;51(6):997-1006 – reference: 24218458 - Circulation. 2013 Dec 17;128(24):2585-94 – reference: 21220308 - Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1705-10 – reference: 17646576 - Circulation. 2007 Jul 31;116(5):463-70 – reference: 21040091 - J Cardiovasc Electrophysiol. 2011 Apr;22(4):448-54 – reference: 17222809 - Cardiovasc Res. 2007 Mar 1;73(4):729-38
SSID	ssj0000391844
Score	2.4024148
Snippet	The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled... The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled...
SourceID	pubmedcentral hal proquest pubmed crossref springer
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	4664
SubjectTerms	14/32 14/34 42/41 631/208/2489/144 631/208/2489/201 631/443/592/75/29 9/74 Animals Arrhythmias, Cardiac - drug therapy Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - physiopathology Benzazepines - pharmacology Calcium Signaling - genetics Cardiology and cardiovascular system Disease Models, Animal Female G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism Genetics Heart Rate - drug effects Human health and pathology Humanities and Social Sciences Humans Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism Inactivation Life Sciences Male Mice Mice, Inbred C57BL Mice, Transgenic multidisciplinary Muscle Proteins - genetics Muscle Proteins - metabolism Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Oocytes - physiology Patch-Clamp Techniques Potassium Channels - genetics Potassium Channels - metabolism Pregnancy Science Science (multidisciplinary) Xenopus
Title	Cardiac arrhythmia induced by genetic silencing of ‘funny’ (f) channels is rescued by GIRK4 inactivation
URI	https://link.springer.com/article/10.1038/ncomms5664 https://www.ncbi.nlm.nih.gov/pubmed/25144323 https://www.proquest.com/docview/1555042957 https://www.proquest.com/docview/1555620511 https://hal.science/hal-01059204 https://pubmed.ncbi.nlm.nih.gov/PMC4207211
Volume	5
WOSCitedRecordID	wos000341057500018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: M~E dateStart: 20100101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre – providerCode: PRVPQU databaseName: Advanced Technologies & Aerospace Database customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: P5Z dateStart: 20100101 isFulltext: true titleUrlDefault: https://search.proquest.com/hightechjournals providerName: ProQuest – providerCode: PRVPQU databaseName: AUTh Library subscriptions: ProQuest Central customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: BENPR dateStart: 20100101 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: M7P dateStart: 20100101 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: 7X7 dateStart: 20100101 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Publicly Available Content Database customDbUrl: eissn: 2041-1723 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000391844 issn: 2041-1723 databaseCode: PIMPY dateStart: 20100101 isFulltext: true titleUrlDefault: http://search.proquest.com/publiccontent providerName: ProQuest
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpR1db9Mw0KIbSLzwDQuMysCksYdoie0k7hMa08YmRhVNgDpeoji2lUhbOpp2Uv89d_kapYgXXioluToX3ffZd0fITsDBp86w82PEhCskS10ZKOsq7QuQJqF5XUj7_Swaj-VkMorbhFvVHqvsdGKtqPU0wxz5Pti9AJVnEH24_uni1CjcXW1HaAzIJnZJQMGMgx99jgW7n0shuq6kXO6XsORVBS6MWLFDgxxPQa67mOsnJf_YLq2t0PHD_8X_EXnQ-p_0oGGYx-SOKZ-Qe81EyuVTkh_WHJPRdDbLl_P8qkgpRO1Af03VkgK3YdEjrQqsVQIM6dTSXbCN5XKXvrd7FOuISzC3tKgoBPLZovnfp9PzzwIWwiqKJgf8jHw7Pvp6eOK2wxjcLBBs7iqIZW3KIxOxAAjIrckiCMTNyNe-CpU1oQyMDlPPeDo1Eq5V6nMLAaYGSG35c7JRTkuzRahUoFZUKIzNMsG9VDFPGQuhlPaUr6TnkL2ONEnWdirHgRmXSb1jzmVyS0aHvOthr5v-HH-FegsU7gGwpfbJwVmC93BC6Ih54sZ3yHZHuaQV5Cq5JZtD3vSPQQRxXyUtzXTRwIQMtBss8aLhl_5V4D4KwRl3SLTCSSu4rD4pi7xu8y0Y9q6DNXc6nvsNrbVPfPlv7F-R--DqCcyGM3-bbMxnC_Oa3M1u5kU1G5JBNInqXzkkmx-PxvH5EE_BxsNaoOBefPolvvgFhCkr4w
linkProvider	ProQuest
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3db9MwED9tAwQvfH8EBhgYGnuIlthOnD4gNA1Gq5YKoYH6FuLYViKxdCTtUP4p_kbOSdNRinjbA49prs45-d35zr4PgJ2AoU2d2sqPgnKXRzRxo0AaVyqfozRxxZpE2i8jMR5Hk0nv4wb87HJhbFhlpxMbRa2mqd0j38d1L7DKMxBvTr-7tmuUPV3tWmi0sBjq-ge6bNXrwVv8vi8pPXp3fNh3F10F3DTgdOZKdMpMwoQWNEBOmNGpQI9S93zly1AaHUaBVmHiaU8lOsJrmfjMoKekkFIZhuNuwiVkRdgQMjERyz0dW2094ryrgsqi_QKncFKhycRX1r3NzEZdrpu065GZfxzPNqve0Y3_7X3dhOsL-5octAJxCzZ0cRuutB036zuQHTYSkZKkLLN6lp3kCckLhfhWRNYEpckmdZIqt7lY-EbI1JBdXPuLepe8MnvE5kkXaE6QvCKlrtJ5-7_3g09DjgPZLJF2j_sufL6Qad6DrWJa6AdAIolqU4ZcmzTlzEsk9aQ26CoqT_oy8hzY66AQp4tK7LYhyLe4iQhgUXwOGwdeLGlP2_ojf6V6johaEtiS4f2DUWx_sx1Qe9TjZ74D2x1S4oWiquJzmDjwbHkbVYw9N0oKPZ23NCFF7Y1D3G_xuXwUmsecM8ocECvIXeFl9U6RZ00Zc05tbT4cc6fD-G9srU3x4b-5fwpX-8cfRvFoMB4-gmto1nK780_9bdialXP9GC6nZ7O8Kp80Ikvg60Vj_hfGeIdq
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB61BSouvAuBAgaKSg9RE9vZZA8IVS1LV7tarRBFFZcQx7YSiWZLsluUv8avY5xXWRZx64FjkoljO9-MZ-x5AOx4DHXq2GR-9Cm3eUAjO_CEtoV0OXITl6wKpP089ieT4PS0P12Dn20sjHGrbGViJajlLDZ75Pu47nlGeKIBrxu3iOnR4N35d9tUkDInrW05jRoiI1X-QPOteDs8wn_9mtLB-0-Hx3ZTYcCOPU7ntkADTUfMVz71sFdMq9hH61L1XemKntCqF3hK9iJHOTJSAV6LyGUarSaJlFIzbHcdrvloYxrDb-p96fZ3TOb1gPM2IyoL9jMczlmB6hNfWgPXE-OBuarernpp_nFUW62Ag9v_89zdgVuN3k0Oaka5C2squwc36kqc5X1IDitOiUmU50k5T87SiKSZRNxLIkqCXGaCPUmRmhgtnB0y02QXdYKs3CVv9B4x8dMZqhkkLUiuinhRv_dh-HHEsSETPVLvfT-AkysZ5hZsZLNMPQISCBSnoseVjmPOnEhQRyiNJqR0hCsCx4K9FhZh3GRoN4VCvoWVpwALwksIWfCqoz2v85L8leoloqsjMKnEjw_GoblnKqP2qcMvXAu2W9SEjQArwkvIWPCie4yix5wnRZmaLWqaHkWpjk08rLHafQrVZs4ZZRb4Syhe6svykyxNqvTmnJqcfdjmTov337q1MsTH_-79c9hEqIfj4WT0BG6itsvNgQB1t2Fjni_UU7geX8zTIn9WcS-Br1cN-V-745Bd
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cardiac+arrhythmia+induced+by+genetic+silencing+of+%27funny%27+%28f%29+channels+is+rescued+by+GIRK4+inactivation&rft.jtitle=Nature+communications&rft.au=Mesirca%2C+Pietro&rft.au=Alig%2C+Jacqueline&rft.au=Torrente%2C+Angelo+G&rft.au=M%C3%BCller%2C+Jana+Christina&rft.date=2014-08-21&rft.pub=Nature+Publishing+Group&rft.eissn=2041-1723&rft.volume=5&rft.spage=4664&rft_id=info:doi/10.1038%2Fncomms5664&rft.externalDBID=HAS_PDF_LINK&rft.externalDocID=3409143881
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2041-1723&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2041-1723&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2041-1723&client=summon