title: Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.
abstract: 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(+)/Ca(2+) exchange (NCX) and Na(+)/K(+)-ATPase (NKA). While the relevance of Ca(2+) 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 Ca(2+) 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(+)/Ca(2+) exchanger (NCX) and the Na(+)/K(+) pump (NKA). By transporting three Na(+) ions into the cytoplasm in exchange for one Ca(2+) 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(+)/Ca(2+) exchanger (NCX1) and Na(+)/K(+) pump and the controversies that still persist in the field.
authors.affiliation: King's College London BHF Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
authors.forename: Michela
authors.initials: M
authors.lastname: Ottolia
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.forename: Mordecai P
authors.initials: MP
authors.lastname: Blaustein
authors.forename: Andrii
authors.initials: A
authors.lastname: Boguslavskyi
authors.forename: Julie
authors.initials: J
authors.lastname: Bossuyt
authors.forename: John H B
authors.initials: JH
authors.lastname: Bridge
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen-Izu
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Clancy
authors.forename: Andrew
authors.initials: A
authors.lastname: Edwards
authors.forename: Joshua
authors.initials: J
authors.lastname: Goldhaber
authors.forename: Jack
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Lingrel
authors.forename: Davor
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Kenneth
authors.initials: K
authors.lastname: Philipson
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Xie
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D003226:Congresses as Topic; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase