Crosstalk between mitochondrial and sarcoplasmic reticulum Ca2+ cycling modulates cardiac pacemaker cell automaticity

Yael Yaniv, Harold A. Spurgeon, Alexey E. Lyashkov, Dongmei Yang, Bruce D. Ziman, Victor A. Maltsev, Edward G. Lakatta

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Article numbere37582
JournalPloS one
Issue number5
StatePublished - May 29 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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