title: Intracellular Na+ regulation in cardiac myocytes.
abstract: Intracellular [Na+] ([Na+]i) is regulated in cardiac myocytes by a balance of Na+ influx and efflux mechanisms. In the normal cell there is a large steady state electrochemical gradient favoring Na+ influx. This potential energy is used by numerous transport mechanisms, including Na+ channels and transporters which couple Na+ influx to either co- or counter-transport of other ions and solutes. Six sarcolemmal Na+ influx pathways are discussed in relatively quantitative terms: Na+ channels, Na+/Ca2+ exchange, Na+/H+ exchange, Na+/Mg2+ exchange, Na+/HCO3- cotransport and Na+/K+/2Cl- cotransport. Under normal conditions Na+/Ca2+ exchange and Na+ channels are the dominant Na+ influx pathways, but other transporters may become increasingly important during altered conditions (e.g. acidosis or cell volume stress). Mitochondria also exhibit Na+/Ca2+ antiporter and Na+/H+ exchange activity that are important in mitochondrial function. These coupled fluxes of Na+ with Ca2+, H+ and HCO3- make the detailed understanding of [Na+]i regulation pivotal to the understanding of both cardiac excitation-contraction coupling and pH regulation. The Na+/K+-ATPase is the main route for Na+ extrusion from cells and [Na+]i is a primary regulator under physiological conditions. [Na+]i is higher in rat than rabbit ventricular myocytes and the reason appears to be higher Na+ influx in rat with a consequent rise in Na+/K+-ATPase activity (rather than lower Na+/K+-ATPase function in rat). This has direct functional consequences. There may also be subcellular [Na+]i gradients locally in ventricular myocytes and this may also have important functional implications. Thus, the balance of Na+ fluxes in heart cells may be complex, but myocyte Na+ regulation is functionally important and merits focused attention as in this issue.
authors.affiliation: Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA. dbers@lumc.edu <dbers@lumc.edu>
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.forename: William H
authors.initials: WH
authors.lastname: Barry
authors.forename: Sanda
authors.initials: S
authors.lastname: Despa
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
chemical_list: D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase