Channelpedia

PubMed 22723299


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.5 , Nav1.8



Title: Blocking scn10a channels in heart reduces late sodium current and is antiarrhythmic.

Authors: Tao Yang, Thomas C Atack, Dina Myers Stroud, Wei Zhang, Lynn Hall, Dan M Roden

Journal, date & volume: Circ. Res., 2012 Jul 20 , 111, 322-32

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22723299


Abstract
Although the sodium channel locus SCN10A has been implicated by genome-wide association studies as a modulator of cardiac electrophysiology, the role of its gene product Nav1.8 as a modulator of cardiac ion currents is unknown.We determined the electrophysiological and pharmacological properties of Nav1.8 in heterologous cell systems and assessed the antiarrhythmic effect of Nav1.8 block on isolated mouse and rabbit ventricular cardiomyocytes.We first demonstrated that Scn10a transcripts are identified in mouse heart and that the blocker A-803467 is highly specific for Nav1.8 current over that of Nav1.5, the canonical cardiac sodium channel encoded by SCN5A. We then showed that low concentrations of A-803467 selectively block "late" sodium current and shorten action potentials in mouse and rabbit cardiomyocytes. Exaggerated late sodium current is known to mediate arrhythmogenic early afterdepolarizations in heart, and these were similarly suppressed by low concentrations of A-803467.Scn10a expression contributes to late sodium current in heart and represents a new target for antiarrhythmic intervention.