Intracellular Ca2+ cycling is a general regulator of how fast and how strong the heart beats

Research output: Contribution to journalArticlepeer-review


Signals for faster and stronger beating of the heart (involving pacemaker cells and ventricular myocytes) are both transduced via common cell effectors, through sequestration and release of Ca2+ to and from sarcoplasmic reticulum (SR). Graded synchronization of local calcium releases (LCRs) from the SR is the basis of graded function within both cell types. An increase in the number of LCRs occurring within a given epoch induces a local recruitment of ryanodine receptors (RyRs) to fire within that epoch in both cell types. In sinoatrial nodal cells (SANC), a high level of basal cAMP-PKA-CaMKII signaling is present, which even in the absence of G protein-coupled receptor (GPCR) stimulation, allows partially synchronized, spontaneous LCRs to normally occur during the diastolic depolarization (DD) between successive action potentials (APs). This amplifies the rate of DD change, prompting surface membranes to generate an AP. Extension of the same basal transduction signaling pathways by GPCR receptor stimulation in SANC effects slower or faster heartbeats, and in ventricular myocytes, changes in synchronization of the functions of Ca2+ cycling molecules occurring in response to GPCR result in stronger or weaker heartbeats. Synchronization of RyR activation and Ca2+ release thus constitutes a unified mechanism that links chronotropy in the heart's pacemaker cells to inotropy in the ventricular cells.

Original languageEnglish (US)
Pages (from-to)253-278
Number of pages26
JournalDialogues in Cardiovascular Medicine
Issue number4
StatePublished - Dec 1 2010
Externally publishedYes


  • Biological clock
  • Chronotropy
  • Heartbeat
  • Inotropy
  • Intracellular calcium clock
  • Pacemaker cell
  • Ryanodine receptor
  • Ventricular cell

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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