| 14976404 |
Shi H, Wang H, Li D, Nattel S, Wang Z: Differential alterations of receptor densities of three muscarinic acetylcholine receptor subtypes and current densities of the corresponding K+ channels in canine atria with atrial fibrillation induced by experimental congestive heart failure. Cell Physiol Biochem. 2004;14(1-2):31-40.
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 IKACh by the M2, and two delayed rectifier K+ currents IKM3 and IK4AP by the M3 and M4 receptors, respectively. We studied the alterations of atrial mAChRs and their coupled K+ channels in the setting of AF in dogs with ventricular tachypacing-induced CHF. Whole-patch-clamp recordings showed that the current densities of IKACh (induced by 1 mM acetylcholine) and IK4AP (induced by 1 mM 4-aminopyridine) were n45% and n55% lower, respectively, while that of IKM3 (induced by 10 mM choline) was n75% higher, at a plateau voltage of 0 mV in atrial myocytes from CHF than those from healthy hearts. In healthy hearts, IKACh comprised > 60%, and IKM3 and IK4AP <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 IKM3 increased to approximately 50%, exceeding those of IKACh or IK4AP. Western blot analyses with atrial membrane protein samples indicated that receptor densities of the M2 and M4 subtypes decreased by approximately 33% and approximately 22%, respectively, whereas that of the M3 subtype increased by approximately 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. |
2(0,0,0,2) |