Indexed on: 15 Feb '17Published on: 15 Feb '17Published in: The Journal of Physiology
Excitation-contraction coupling (ECC) is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca(2+) across the sarcolemma triggering Ca(2+) release from the sarcoplasmic reticulum (SR) - a process termed Ca(2+) -induced Ca(2+) release (CICR) - followed by re-sequestration of Ca(2+) into the SR. The sodium calcium exchanger (NCX) inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. Thus, influx of Na(+) via voltage-gated Na(+) channels (NaV ) has emerged as an important regulator of CICR both in health and in disease. Recent insights into the subcellular distribution of cardiac and neuronal NaV isoforms and their ultrastructural milieu have important implications for the roles of these channels in mediating Ca(2+) -driven arrhythmias. This review will discuss functional insights into the role of neuronal NaV isoforms vis-à-vis cardiac NaV s in triggering such arrhythmias and their potential as therapeutic targets in the context of the aforementioned structural observations. This article is protected by copyright. All rights reserved.