© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Intracellular Na+ regulation in cardiac myocytes
aDepartment of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
bDivision of Cardiology, University of Utah, Health Science Center, Salt Lake City, UT 84132, USA
* Corresponding author. Tel.: +1-708-216-1018; fax: +1-708-216-6308. dbers{at}lumc.edu
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.
KEYWORDS Myocytes; Na/Ca-exchanger; Na/H-exchanger; Na/K-pump; Na-channel
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|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
A. J Workman, K. A Kane, and A. C Rankin Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation Cardiovasc Res, September 1, 2003; 59(3): 593 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske, S. R Houser, G. Hasenfuss, and D. M Bers Sodium and the heart: a hidden key factor in cardiac regulation Cardiovasc Res, March 15, 2003; 57(4): 871 - 872. [Full Text] [PDF]
|
|