Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage

CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3...

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Vydáno v:	eLife Ročník 6
Hlavní autoři:	Vivas, Oscar, Moreno, Claudia M, Santana, Luis F, Hille, Bertil
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cambridge eLife Sciences Publications Ltd 30.06.2017 eLife Sciences Publications, Ltd
Témata:	Biophysics and Structural Biology BK channels Calcium channels (voltage-gated) Calcium influx Channel gating Excitability ground-state depletion hippocampal neurons Hippocampus Hypotheses Immunoglobulins Localization Physiology Plasmids Potassium Potassium channels (calcium-gated) Software super-resolution microscopy Sympathetic nerves sympathetic neurons voltage-gated calcium channels
ISSN:	2050-084X, 2050-084X
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Abstract	CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.
AbstractList	CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near -50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near -50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. DOI: http://dx.doi.org/10.7554/eLife.28029.001 CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.DOI: http://dx.doi.org/10.7554/eLife.28029.001
Author	Moreno, Claudia M Vivas, Oscar Hille, Bertil Santana, Luis F
Author_xml	– sequence: 1 givenname: Oscar orcidid: 0000-0002-0964-385X surname: Vivas fullname: Vivas, Oscar organization: Department of Physiology and Biophysics, University of Washington, Seattle, United States, Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States – sequence: 2 givenname: Claudia M surname: Moreno fullname: Moreno, Claudia M organization: Department of Physiology and Biophysics, University of Washington, Seattle, United States, Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States – sequence: 3 givenname: Luis F orcidid: 0000-0002-4297-8029 surname: Santana fullname: Santana, Luis F organization: Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States – sequence: 4 givenname: Bertil surname: Hille fullname: Hille, Bertil organization: Department of Physiology and Biophysics, University of Washington, Seattle, United States
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Snippet	CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional...
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SubjectTerms	Biophysics and Structural Biology BK channels Calcium channels (voltage-gated) Calcium influx Channel gating Excitability ground-state depletion hippocampal neurons Hippocampus Hypotheses Immunoglobulins Localization Physiology Plasmids Potassium Potassium channels (calcium-gated) Software super-resolution microscopy Sympathetic nerves sympathetic neurons voltage-gated calcium channels
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Title	Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage
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