Crosstalk between Mitochondrial and Sarcoplasmic Reticulum Ca2+ Cycling Modulates Cardiac Pacemaker Cell Automaticity

Mitochondria dynamically buffer cytosolic Ca(2+) in cardiac ventricular cells and this affects the Ca(2+) load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca(2+) releases (LCRs) that depend upon the SR load and are involved in S...

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Published in:PloS one Vol. 7; no. 5; p. e37582
Main Authors: Yaniv, Yael, Spurgeon, Harold A., Lyashkov, Alexey E., Yang, Dongmei, Ziman, Bruce D., Maltsev, Victor A., Lakatta, Edward G.
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.05.2012
Public Library of Science (PLoS)
Subjects:
Action potential
Action Potentials - drug effects
Aging
Animals
Automation
Biology
Calcium (mitochondrial)
Calcium (reticular)
Calcium - metabolism
Calcium buffering
Calcium efflux
Calcium influx
Calcium signalling
Cardiac muscle
Clonazepam - analogs & derivatives
Clonazepam - pharmacology
Computer Science
Confocal
Crosstalk
Cytosol - drug effects
Cytosol - metabolism
Depolarization
Efflux
Electric Conductivity
Firing rate
Heart
Heart diseases
Heart Rate - drug effects
Heart Ventricles - cytology
Indoles - metabolism
Inhibition
Ion channels
Kinases
Laboratories
Magnesium - pharmacology
Medicine
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Models, Biological
Myocytes, Cardiac - cytology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Periodicity
Permeability
Predictive control
Rabbits
Rodents
Ruthenium Compounds - pharmacology
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcoplasmic reticulum
Sarcoplasmic Reticulum - drug effects
Sarcoplasmic Reticulum - metabolism
Science
Sinoatrial Node - cytology
Sinoatrial Node - drug effects
Sinoatrial Node - metabolism
Sinoatrial Node - physiology
Thiazepines - pharmacology
Ventricle
United States > US
Maryland
Baltimore Maryland
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Mitochondria dynamically buffer cytosolic Ca(2+) in cardiac ventricular cells and this affects the Ca(2+) load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca(2+) releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na(+)-Ca(2+) exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP). To determine if mitochondrial Ca(2+) (Ca(2+) (m)), cytosolic Ca(2+) (Ca(2+) (c))-SR-Ca(2+) crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity. Inhibition of mitochondrial Ca(2+) influx into (Ru360) or Ca(2+) efflux from (CGP-37157) decreased [Ca(2+)](m) to 80 ± 8% control or increased [Ca(2+)](m) to 119 ± 7% control, respectively. Concurrent with inhibition of mitochondrial Ca(2+) influx or efflux, the SR Ca(2+) load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca(2+) signal were highly correlated with the change in the SR Ca(2+) load (r(2) = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111 ± 1% control; CGP-37157, 89 ± 2% control) in response to changes in [Ca(2+)](m) were predicted by concurrent changes in LCR period (r(2) = 0.84). A change in SANC Ca(2+) (m) flux translates into a change in the AP firing rate by effecting changes in Ca(2+) (c) and SR Ca(2+) loading, which affects the characteristics of spontaneous SR Ca(2+) release.
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Conceived and designed the experiments: EGL YY. Performed the experiments: YY AEL DY. Analyzed the data: YY AEL. Contributed reagents/materials/analysis tools: HAS BDZ VAM. Wrote the paper: EGL YY.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0037582