The calcium and voltage clocks in sinoatrial node automaticity

Boyoung Joung, Masahiro Ogawa, Shien-Fong Lin, Peng Sheng Chen*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


Recent evidence indicates that the voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. Since the intact SAN is a heterogeneous structure that includes multiple different cell types interacting with each other, the relative importance of the voltage and Ca2+ clocks for pacemaking may be variable in different regions of the SAN. Recently, we performed optical mapping in isolated and Langendorff-perfused canine right atria. We mapped the intracellular calcium (Cai) and membrane potentials of the intact SAN simultaneously. Using previously described criteria of the timing of the late diastolic Cai elevation (LDCAE) relative to the action potential upstroke to detect Ca2+ clock activity, we demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with the robust LDCAE during β-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic SR Ca 2+ release and was closely related with heart rate changes. We conclude that the Ca and voltage clocks work synergistically to generate SAN automaticity.

Original languageEnglish
Pages (from-to)217-222
Number of pages6
JournalKorean Circulation Journal
Issue number6
StatePublished - Jun 2009


  • Calcium
  • Sarcoplasmic reticulum
  • Sinoatrial node
  • Sympathetic nervous system


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