Beat-to-beat Ca 2+-dependent regulation of sinoatrial nodal pacemaker cell rate and rhythm

Yael Yaniv, Victor A. Maltsev, Ariel L. Escobar, Harold A. Spurgeon, Bruce D. Ziman, Michael D. Stern, Edward Lakatta

Research output: Contribution to journalArticle

Abstract

Whether intracellular Ca 2+ regulates sinoatrial node cell (SANC) action potential (AP) firing rate on a beat-to-beat basis is controversial. To directly test the hypothesis of beat-to-beat intracellular Ca 2+ regulation of the rate and rhythm of SANC we loaded single isolated SANC with a caged Ca 2+ buffer, NP-EGTA, and simultaneously recorded membrane potential and intracellular Ca 2+. Prior to introduction of the caged Ca 2+ buffer, spontaneous local Ca 2+ releases (LCRs) during diastolic depolarization were tightly coupled to rhythmic APs (r 2=0.9). The buffer markedly prolonged the decay time (T 50) and moderately reduced the amplitude of the AP-induced Ca 2+ transient and partially depleted the SR load, suppressed spontaneous diastolic LCRs and uncoupled them from AP generation, and caused AP firing to become markedly slower and dysrhythmic. When Ca 2+ was acutely released from the caged compound by flash photolysis, intracellular Ca 2+ dynamics were acutely restored and rhythmic APs resumed immediately at a normal rate. After a few rhythmic cycles, however, these effects of the flash waned as interference with Ca 2+ dynamics by the caged buffer was reestablished. Our results directly support the hypothesis that intracellular Ca 2+ regulates normal SANC automaticity on a beat-to-beat basis.

Original languageEnglish (US)
Pages (from-to)902-905
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number6
DOIs
StatePublished - Dec 2011
Externally publishedYes

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Sinoatrial Node
Action Potentials
Buffers
Photolysis
Membrane Potentials

Keywords

  • Arrhythmia
  • Ca2+-excitation contraction coupling
  • Ca cycling
  • Pacemaker Ca2+ clock
  • Pacemaker cell automaticity

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Beat-to-beat Ca 2+-dependent regulation of sinoatrial nodal pacemaker cell rate and rhythm. / Yaniv, Yael; Maltsev, Victor A.; Escobar, Ariel L.; Spurgeon, Harold A.; Ziman, Bruce D.; Stern, Michael D.; Lakatta, Edward.

In: Journal of Molecular and Cellular Cardiology, Vol. 51, No. 6, 12.2011, p. 902-905.

Research output: Contribution to journalArticle

Yaniv, Yael ; Maltsev, Victor A. ; Escobar, Ariel L. ; Spurgeon, Harold A. ; Ziman, Bruce D. ; Stern, Michael D. ; Lakatta, Edward. / Beat-to-beat Ca 2+-dependent regulation of sinoatrial nodal pacemaker cell rate and rhythm. In: Journal of Molecular and Cellular Cardiology. 2011 ; Vol. 51, No. 6. pp. 902-905.
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