期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 14, 期 1-2, 页码 31-40出版社
KARGER
DOI: 10.1159/000076924
关键词
muscarinic acetylcholine receptors; M-2 receptor; M-3 receptor; M-4 receptor; I-KACh, I-KM3, I-K4AP; canine atrial myocyte; atrial fibrillation; congestive heart failure
Parasympathetic tone and congestive heart failure (CHF) are two of promoting factors in initiation and perpetuation of atrial fibrillation (AF). Recent studies indicate co-existence of multiple muscarinic acetylcholine receptor subtypes (mAChRs) that mediate several distinct K+ currents in the heart; inward rectifier K+ current I-KACh by the M-2, and two delayed rectifier K+ currents I-KM3 and I-K4AP by the M-3 and M-4 receptors, respectively. We studied the alterations of atrial mAChRs and their coupled K+ channels in the setting of AF in dogs with ventricular tachypacing-incluced CHF. Whole-patch-clamp recordings showed that the current densities of I-KACh (induced by 1 mM acetylcholine) and I-K4AP (induced by 1 mM 4-aminopyridine) were similar to45% and similar to55% lower, respectively, while that of I-KM3 (induced by 10 mM choline) was similar to75% higher, at a plateau voltage of 0 mV in atrial myocytes from CHF than those from healthy hearts. In healthy hearts, I-KACh comprised >60%, and I-KM3 and I-K4AP <30%, of the total outward K+ currents mediated by mAChRs at depolarized potentials (between -20 mV and +50 mV). In AF atria of CHF dogs, however, the contribution of I-KM3 increased to similar to 50%, exceeding those of I-KACh or I-K4AP. Western blot analyses with atrial membrane protein samples indicated that receptor densities of the M-2 and M-4 subtypes decreased by similar to 33% and similar to 22%, respectively, whereas that of the M-3 subtype increased by similar to 2.3 folds, in parallel to the alterations of the corresponding K+ currents. We conclude that differential alterations of mAChR subtypes underlie differential alterations of their coupled K channels in AF atria and these differential alterations may contribute to atrial remodeling in AF induced in the setting of CHF. Copyright (C) 2004 S. Karger AG, Basel.
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