Mechanisms underlying the cardiac pacemaker: The role of SK4 calcium-activated potassium channels

David Weisbrod, Shiraz Haron Khun, Hanna Bueno, Asher Peretz, Bernard Attali*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca 2+ -activated K + channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

Original languageEnglish
Pages (from-to)82-97
Number of pages16
JournalActa Pharmacologica Sinica
Issue number1
StatePublished - 1 Jan 2016


  • Ca2+ clock model
  • SK4 K+ channel
  • cardiac pacemaker
  • sinoatrial node
  • voltage clock model


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