TY - JOUR
T1 - Crosstalk between mitochondrial and sarcoplasmic reticulum Ca2+ cycling modulates cardiac pacemaker cell automaticity
AU - Yaniv, Yael
AU - Spurgeon, Harold A.
AU - Lyashkov, Alexey E.
AU - Yang, Dongmei
AU - Ziman, Bruce D.
AU - Maltsev, Victor A.
AU - Lakatta, Edward G.
PY - 2012/5/29
Y1 - 2012/5/29
N2 - Background: Mitochondria dynamically buffer cytosolic Ca2+ in cardiac ventricular cells and this affects the Ca2+ load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca2+ releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na+-Ca2+ exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP). Objective: To determine if mitochondrial Ca2+ (Ca2+m), cytosolic Ca2+ (Ca2+c)-SR-Ca2+ crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity. Results: Inhibition of mitochondrial Ca2+ influx into (Ru360) or Ca2+ efflux from (CGP-37157) decreased [Ca2+]m to 80±8% control or increased [Ca2+]m to 119±7% control, respectively. Concurrent with inhibition of mitochondrial Ca2+ influx or efflux, the SR Ca2+ load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca2+ signal were highly correlated with the change in the SR Ca2+ load (r2 = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111±1% control; CGP-37157, 89±2% control) in response to changes in [Ca2+]m were predicted by concurrent changes in LCR period (r2 = 0.84). Conclusion: A change in SANC Ca2+m flux translates into a change in the AP firing rate by effecting changes in Ca2+c and SR Ca2+ loading, which affects the characteristics of spontaneous SR Ca2+ release.
AB - Background: Mitochondria dynamically buffer cytosolic Ca2+ in cardiac ventricular cells and this affects the Ca2+ load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca2+ releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na+-Ca2+ exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP). Objective: To determine if mitochondrial Ca2+ (Ca2+m), cytosolic Ca2+ (Ca2+c)-SR-Ca2+ crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity. Results: Inhibition of mitochondrial Ca2+ influx into (Ru360) or Ca2+ efflux from (CGP-37157) decreased [Ca2+]m to 80±8% control or increased [Ca2+]m to 119±7% control, respectively. Concurrent with inhibition of mitochondrial Ca2+ influx or efflux, the SR Ca2+ load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca2+ signal were highly correlated with the change in the SR Ca2+ load (r2 = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111±1% control; CGP-37157, 89±2% control) in response to changes in [Ca2+]m were predicted by concurrent changes in LCR period (r2 = 0.84). Conclusion: A change in SANC Ca2+m flux translates into a change in the AP firing rate by effecting changes in Ca2+c and SR Ca2+ loading, which affects the characteristics of spontaneous SR Ca2+ release.
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U2 - 10.1371/journal.pone.0037582
DO - 10.1371/journal.pone.0037582
M3 - Article
C2 - 22666369
AN - SCOPUS:84861551026
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 5
M1 - e37582
ER -