Na+/Ca2+ exchange and Na+/K+-ATPase in the heart

Michael J. Shattock, Michela Ottolia, Donald M. Bers, Mordecai P. Blaustein, Andrii Boguslavskyi, Julie Bossuyt, John H. B. Bridge , Ye Chen‐Izu , Colleen E. Clancy , Andrew Edwards , Joushua Goldhaber, Jack Kaplan, Jerry B. Lingrel, Davor Pavlovic, Kenneth Philipson , Karin R. Sipido, Zi‐Jian Xie

Research output: Contribution to journalBook/Film/Article reviewpeer-review

161 Citations (Scopus)
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This paper is the third in a series of reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation–contraction coupling and arrhythmias: Na+ channel and Na+ transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on cardiac Na+/Ca2+ exchange (NCX) and Na+/K+‐ATPase (NKA). While the relevance of Ca2+ homeostasis in cardiac function has been extensively investigated, the role of Na+ regulation in shaping heart function is often overlooked. Small changes in the cytoplasmic Na+ content have multiple effects on the heart by influencing intracellular Ca2+ and pH levels thereby modulating heart contractility. Therefore it is essential for heart cells to maintain Na+ homeostasis. Among the proteins that accomplish this task are the Na+/Ca2+ exchanger (NCX) and the Na+/K+ pump (NKA). By transporting three Na+ ions into the cytoplasm in exchange for one Ca2+ moved out, NCX is one of the main Na+ influx mechanisms in cardiomyocytes. Acting in the opposite direction, NKA moves Na+ ions from the cytoplasm to the extracellular space against their gradient by utilizing the energy released from ATP hydrolysis. A fine balance between these two processes controls the net amount of intracellular Na+ and aberrations in either of these two systems can have a large impact on cardiac contractility. Due to the relevant role of these two proteins in Na+ homeostasis, the emphasis of this review is on recent developments regarding the cardiac Na+/Ca2+ exchanger (NCX1) and Na+/K+ pump and the controversies that still persist in the field.
Original languageEnglish
Pages (from-to)1361-1382
Number of pages21
JournalJournal of Physiology
Issue number6
Early online date13 Mar 2015
Publication statusPublished - 15 Mar 2015


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