Sodium and the heart: a hidden key factor in cardiac regulation

Abstract

Myocyte Na+ homeostasis is crucially involved in a number of vital cell functions, such as excitability, excitation–contraction coupling, energy metabolism, pH regulation, as well as cardiac development and growth. However, consideration of Na+ regulation is often relegated to a secondary position in the discussion of cardiac (patho-)physiology, where the focus is typically on contractile proteins, Ca2+ regulation and pH regulation which appear more directly related to contractile function. However, myocyte Na+ homeostasis is as complex as Ca2+ or pH homeostasis and [Na+]i very directly influences intracellular [Ca2+] and pH via powerful cardiac Na/Ca exchange, Na/H exchange and Na-bicarbonate cotransport systems. Na+ flux my even be central in mediating effects of mechanical loading of the heart on excitation–contraction coupling. Moreover, [Na+]i homeostasis is regulated by a delicate balance of Na+ channels and transporters in the surface and mitochondrial membrane that maintain a large [Na+] gradient across the sarcolemmal membrane. Given this fundamental but often overlooked contribution of Na … * Corresponding author. Tel.: +49-551-3989-25; fax: +49-551-3919-127.