Abstract
Excitation-contraction coupling 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 Na(+) /Ca(2+) exchanger inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. Thus, influx of Na(+) via voltage-gated Na(+) channels (Na(V) ) has emerged as an important regulator of CICR both in health and in disease. Recent insights into the subcellular distribution of cardiac and neuronal Na(V) 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 Na(V) isoforms vis-à-vis cardiac Na(V) s in triggering such arrhythmias and their potential as therapeutic targets in the context of the aforementioned structural observations.