Cardiac sodium channels: Dysregulation meets myocardial failure

Abstract

See article by Hesse et al. [12] (pages 498–509) in this issue. Within the orchestra of cardiac ion channels, voltage–gated Na+ channels have a key function in the determination of the amplitude and slope of the action potential upstroke. Both are important in the control of impulse conduction velocity and maintenance of appropriate waves of excitation through the working myocardium. The main (α-) subunit of the cardiac sodium channel is encoded by the SCN5A (Nav1.5) gene, and the INa current mediated is responsible for the membrane depolarization. Fast inactivation of sodium channels appears within milliseconds, and the vast majority of sodium channels transit from the open state to a non-conductive state. Gating dysfunction or changes in the number of functional channels of cardiac sodium channels are linked to several cardiac arrhythmias [1–4]. Meanwhile, more than 170 different SCN5A mutations have been reported (currently, 77 for LQT-3, 90 for Brugada syndrome, 10 for conduction disease; see http://www.fsm.it/cardmoc/), and this has enabled evaluation of structure-function relationships of the sodium channel. Analysis of several of these mutations has consistently demonstrated that loss of function is the … * Tel.: +49 251 83 529 82; fax: +49 251 83 575 70. Eric.Schulze-Bahr{at}ukmuenster.de