If and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells

Zhan Gao, Biyi Chen, Mei ling A. Joiner, Yuejin Wu, Xiaoqun Guan, Olha M. Koval, Ashok K. Chaudhary, Shane R. Cunha, Peter J. Mohler, James B. Martins, Long Sheng Song, Mark E. Anderson

Research output: Contribution to journalArticlepeer-review


Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a 'voltage clock' and a Ca2+ dependent process, or 'Ca2+ clock.' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (If) is thought to be particularly important. A Ca2+ dependent process triggers APs when sarcoplasmic reticulum (SR) Ca2+ release activates inward current carried by the forward mode of the electrogenic Na+/Ca2+ exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca2+ clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective If antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest (~14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca2+ release, but did not affect basal or isoproterenol-enhanced If. Taken together, these results indicate that voltage and Ca2+ dependent automaticity mechanisms coexist in canine SAN cells, and suggest that If and SR Ca2+ release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Issue number1
StatePublished - Jul 2010
Externally publishedYes


  • Action potentials
  • Funny current
  • Pacemaker
  • Sarcoplasmic reticulum
  • Sinoatrial node cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'If and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells'. Together they form a unique fingerprint.

Cite this