title: Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.
abstract: 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.
authors.affiliation: Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Weisbrod
authors.affiliation: Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Shiraz Haron
authors.initials: SH
authors.lastname: Khun
authors.affiliation: Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Bueno
authors.affiliation: Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Peretz
authors.affiliation: Department of Physiology & Pharmacology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Bernard
authors.initials: B
authors.lastname: Attali
mesh_terms: D001683:Biological Clocks; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D012849:Sinoatrial Node / Q000502:physiology*
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D024681:Potassium Channels, Calcium-Activated