Age-related changes in the atrial muscarinic type 2 receptor and their effects on atrial fibrillation vulnerability in rabbits

Aging plays an important role in increased vulnerability to atrial fibrillation (AF). Mediated by activity at the muscarinic type 2 receptor (M2R), the parasympathetic nerve contributes to the onset of AF. The purpose of this study was to investigate whether aging changes the distribution of M2R in the atrial myocardium and to determine the impact of these changes on AF vulnerability. Expression of M2R in the atria] myocardium was evaluated by immunostaining and Western blot in three groups-young (3 months old), mature (8 months old) and senescent (36-48 months old) rabbits. AF inducibility was recorded with and without cervical vagal stimulation (VS) in vivo in all groups. AF inducibility, the atrial effective refractory period (AERP) and the monophasic action potential (MAP) were recorded in an additional seven senescent rabbits before and after topical administration of tropicamide. The results showed that the density of M2R in the left atrial free wall (LAFW) was significantly higher than that in other parts of the atria. The left atrial appendage had a higher level of M2R expression than the right atrium. The M2R density of the epicardial side was greater than that of endocardial side in both atria. The senescent group had a significant increase in M2R expression in the LAFW relative to the mature group. AF inducibility was also higher in the senescent group than in the other two groups. After tropicamide administration in the senescent rabbits, AF inducibility decreased significantly, the VS-induced decrease in AERP and MAP duration at 90% repolarization (MAPD90) of LAFW was attenuated, and the dispersion of the AERP and MAPD90 increase was attenuated. In conclusion, our results suggested that there is spatial heterogeneity in the M2R distribution in the atria of the rabbit. The density of M2R in the LAFW increased with the aging of rabbits. This change in M2R enhanced the heterogeneity of the M2R distribution and contributed to the change in age-related AF vulnerability. (C) 2009 Elsevier Inc. All rights reserved.