Na+ transport in cardiac myocytes; implications for excitation-contraction coupling

Abstract

Intracellular Na+ concentration ([Na+]i) is very important in modulating the contractile and electrical activity of the heart. Upon electrical excitation of the myocardium, voltage-dependent Na + channels open, triggering the upstroke of the action potential (AP). During the AP, Ca2+ enters the myocytes via L-type Ca 2+ channels. This triggers Ca2+ release from the sarcoplasmic reticulum (SR) and thus activates contraction. Relaxation occurs when cytosolic Ca2+ declines, mainly due to re-uptake into the SR via SR Ca2+-ATPase and extrusion from the cell via the Na +/Ca2+ exchanger (NCX). NCX extrudes one Ca2+ ion in exchange for three Na+ ions and its activity is critically regulated by [Na+]i. Thus, via NCX, [Na+] i is centrally involved in the regulation of intracellular [Ca 2+] and contractility. Na+ brought in by Na+ channels, NCX and other Na+ entry pathways is extruded by the Na +/K+ pump (NKA) to keep [Na+]i low. NKA is regulated by phospholemman, a small sarcolemmal protein that associates with NKA. Unphosphorylated phospholemman inhibits NKA by decreasing the pump affinity for internal Na+ and this inhibition is relieved upon phosphorylation. Here we discuss the main characteristics of the Na+ transport pathways in cardiac myocytes and their physiological and pathophysiological relevance. © 2009 IUBMB.