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Voigt, N; Heijman, J; Trausch, A; Mintert-Jancke, E; Pott, L; Ravens, U; Dobrev, D.
Impaired Na⁺-dependent regulation of acetylcholine-activated inward-rectifier K⁺ current modulates action potential rate dependence in patients with chronic atrial fibrillation
J MOL CELL CARDIOL. 2013; 61: 142-152. Doi: 10.1016/j.yjmcc.2013.03.011
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Leading authors Med Uni Graz: Heijman Jordi
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Abstract:: Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor-activated inward-rectifier K+ currents (I-K1 and I-K,I-ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na+ ([Na+](i)) enhances I-K,I-ACh in experimental models but the effect of [Na+](i)-dependent regulation of inward-rectifier K+ currents on APD in human atrial myocytes is currently unknown. Here, we report a [Na+](i)-dependent inhibition of outward I-K1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, I-K,I-ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na+](i) in SR. This [Na+](i)-dependent I-K,I-ACh regulation was absent in cAF. Including [Na+](i) dependence of I-K1 and I-K,I-ACh in a recent computational model of the human atrial myocyte revealed that [Na+](i) accumulation at fast rates inhibits I-K1 and blunts physiological APD rate dependence in both groups. [Na+](i)-dependent I-K,I-ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na+-sensitivity of I-K,I-ACh as one potential mechanism contributing to the blunted APD rate dependence in patients with cAF. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Find related publications in this database (Keywords): Action potential; Atrial fibrillation; Inward-rectifier K+ current; Na+