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The Cardiac Pacemaker Story—Fundamental Role of the Na+/Ca2+ Exchanger in Spontaneous Automaticity

Kohajda, Z.; Loewe, A. ORCID iD icon 1; Tóth, N.; Varró, A.; Nagy, N.
1 Institut für Biomedizinische Technik (IBT), Karlsruher Institut für Technologie (KIT)


The electrophysiological mechanism of the sinus node automaticity was previously considered exclusively regulated by the so-called “funny current”. However, parallel investigations increasingly emphasized the importance of the Ca$^{2+}$-homeostasis and Na+/ Ca$^{2+}$ exchanger (NCX). Recently, increasing experimental evidence, as well as insight through mechanistic in silico modeling demonstrates the crucial role of the exchanger in sinus node pacemaking. NCX had a key role in the exciting story of discovery of sinus node pacemaking mechanisms, which recently settled with a consensus on the coupled-clock mechanism after decades of debate. This review focuses on the role of the Na$^{+}$/Ca$^{2+}$ exchanger from the early results and concepts to recent advances and attempts to give a balanced summary of the characteristics of the local, spontaneous, and rhythmic Ca$^{2+}$ releases, the molecular control of the NCX and its role in the fight-or-flight response. Transgenic animal models and pharmacological manipulation of intracellular Ca$^{2+}$ concentration and/or NCX demonstrate the pivotal function of the exchanger in sinus node automaticity. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000119893
Veröffentlicht am 22.06.2020
DOI: 10.3389/fphar.2020.00516
Zitationen: 9
Web of Science
Zitationen: 7
Zitationen: 11
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biomedizinische Technik (IBT)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 28.04.2020
Sprache Englisch
Identifikator ISSN: 1663-9812
KITopen-ID: 1000119893
Erschienen in Frontiers in pharmacology
Verlag Frontiers Media
Band 11
Seiten Art. Nr.: 516
Schlagwörter Na+/Ca2+ exchanger, pacemaking, sinus node, automaticity, Ca2+-handling
Nachgewiesen in Dimensions
Web of Science
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