HETEROGENEOUS DISTRIBUTION OF THE MUSCARINIC K+ CHANNELS IN GUINEA-PIG ATRIA

摘要

Vagal stimulation can initiate and maintain the atrial fibrillation (AF) by increasing the heterogeneity of the effective refractory period (ERP) in atria. The muscarinic K~+ channel (I_(K,ACh)) represents a relevant target for the action of vagal neurotransmitter acetylcholine (ACh) and its activation should be involved in the alterations of repolarization process in atria associated with an elevation of the vagal tone. The present study was designed to examine the distribution of I_(K,ACh)in different regions of guinea-pig atria clamped using the whole-cell patch-clamp technique. I_(K,ACh) was maximally activated by 10 muM ACh in atrial myocytes isolated from sino-atrial node (SA), right atrial appendage (RAA), right atrial free wall (RA), intraatrial septum (IAS), left atrial appendage (LAA) and left atrial free wall (LA). The densities of I_(K,ACh) at -40 mV were 32.9 +- 6.7 (n = 5), 30.0 +- 9.7 (n = 4), 26.8 +- 6.5 (n = 5), 14.9 +- 7.4 (n = 5), 15.0 +- 7.5 (n = 6) and 19.5 +- 8.3 (n = 5) pA/pF for SA, RAA, RA, IAS, LAA and LA, respectively. These regional differences in I_(K,ACh) density may contribute at least partly to the heterogeneity in repolarization process in atria involved in the vagally-induced AF.