Mechanisms of spontaneous pacing: sinoatrial nodal cells, neonatal cardiomyocytes, and human stem cell derived cardiomyocytes

Canadian Journal of Physiology and Pharmacology
M Morad, Xiao-Hua Zhang

Abstract

The sinoatrial (SA) node is the primary site from which the mammalian heart is paced, but the mechanisms underlying the pacemaking still remain clouded. It is generally believed that the hyperpolarization-activated current If, encoded by hyperpolarization-activated cyclic nucleotide-gated (HCN) genes, contributes significantly to pacing, which in tandem with inward current generated by efflux of Ca2+ via the Na+-Ca2+ exchanger (NCX), resulting from the released Ca2+, mediates the diastolic depolarization. Here, we review the data that implicate If as the "pacemaker current" and conclude that there is not only a significant discrepancy between the range of diastolic depolarization potential (-60 to -40 mV) and the activation potential of If (negative to -70 mV), but that also the kinetics of If and its pharmacology are incompatible with the frequency of a heartbeat in rodents and humans. We propose that If serves as a functional insulator, which protects the SA-nodal cells against the large negative electrical sink of atrial tissue connected to it with connexins. We also evaluate the role of If and calcium signaling in mediating the diastolic depolarization in rat neonatal cardiomyocytes (rN-CM), and human induced pluripotent st...Continue Reading

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Citations

May 11, 2018·Scientific Reports·Manelle RamadanNikki Gillum Posnack
May 20, 2020·Pflügers Archiv : European journal of physiology·Ilaria RivoltaJacopo C DiFrancesco
Jan 28, 2021·Clinical Endocrinology·Abdelwahab Jalal EldinElif A Oral
May 7, 2021·Seminars in Cell & Developmental Biology·Sean A MurphyChulan Kwon
Jun 22, 2021·Progress in Biophysics and Molecular Biology·Maaike HoekstraArie O Verkerk
Jul 26, 2021·Progress in Biophysics and Molecular Biology·Valentina BalducciElisabetta Cerbai

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