Referenced in: none

Automatically associated channels: Nav1.5

Title: Altered Na(+) currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium.

Authors: Samuel Sossalla, Birte Kallmeyer, Stefan Wagner, Marek Mazur, Ulrike Maurer, Karl Toischer, Jan D Schmitto, Ralf Seipelt, Friedrich A Schöndube, Gerd Hasenfuss, Luiz Belardinelli, Lars S Maier

Journal, date & volume: J. Am. Coll. Cardiol., 2010 May 25 , 55, 2330-42

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20488304

Abstract
We investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium.Electrical remodeling during AF is typically associated with alterations in Ca(2+) and K(+) currents. It remains unclear whether I(Na) is also altered.Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied.Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I(Na) density ( approximately 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I(Na) was significantly increased in myocytes from AF atria by approximately 26%. Ran (10 mumol/l) decreased late I(Na) by approximately 60% (p < 0.05) in myocytes from patients with AF but only by approximately 18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca(2+)](o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients.Na(+) channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I(Na) with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I(Na) may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction.