Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8475166 | Journal of Molecular and Cellular Cardiology | 2013 | 11 Pages |
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 (IK1 and IK,ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na+ ([Na+]i) enhances IK,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 IK1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na+]i in SR. This [Na+]i-dependent IK,ACh regulation was absent in cAF. Including [Na+]i dependence of IK1 and IK,ACh in a recent computational model of the human atrial myocyte revealed that [Na+]i accumulation at fast rates inhibits IK1 and blunts physiological APD rate dependence in both groups. [Na+]i-dependent IK,ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na+-sensitivity of IK,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”.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Niels Voigt, Jordi Heijman, Anne Trausch, Elisa Mintert-Jancke, Lutz Pott, Ursula Ravens, Dobromir Dobrev,