Desensitization of muscarinic potassium current and cholinergic stimulation in atrial fibrillation

【Author】

BOYETT Mark;

【Abstract】

<正>Vagal stimulation(VS)and the pulmonary vein sleeves(PVS)play an important role in atrial fibrillation (AF).During continuous VS,the effects of VS on the heart fade with time.This is known as desensitization that can occur in vivo especially in the case of parasympathetic predominance or ageing.In this study,a set of modified bipolar electrodes was used to record extracellular potentials in PVS region and left atrial free wall of rabbit heart perfused physiologically in vitro.The results showed that:(1)in the absence of ACh,burst pacing(7Hz)induced atrial fibrillation(AF)in the PVS region,but not in the left atrial free wall;(2)without burst pacing,ACh induced AF in both PVS region and left atrial free wall,but the ACh-induced AF occurred earlier(2.7±0.4 s,n=8)in the PVS region than in the left atrial free wall;(3)during the application of 5μmol/L ACh,the AF declined with time as a result of desensitization,and the ACh-induced AF disappeared later(9.3±0.5 s,n=8)in the PVS region than in the left atrial free wall;and(4)during the continued presence of ACh,after the disappearance of the ACh-induced AF, burst pacing induced AF in both regions,but the AF was greater in the PVS region than in the left atrial free wall.To study desensitization of muscarinic K~+ current(I_(K,ACh)),whole-cell configuration was used to record I_(K,ACh) of single myocytes from PVS and left atrium,as well as atrial myocytes from patients with and without AF.Our preliminary results showed that:(1)I_(K,ACh)desensitization during 30 s application of 10μmol/L ACh was higher(16.2%,n=5- 17)in myocytes from PVS than from left atrium;(2)peak I_(K,ACh) in atrial myocytes from elder patients(>60years) with chronic AF was lower(5.1 pA/pF,n=7-11)than from elder patients(>60years)with sinus rhythm(SR);(3) peak I_(K,ACh)in younger patients(<40years)with SR was higher(4.3 pA/pF,n= 11-25)than from the elder patients with SR;and(4)I_(K,ACh)desensitization during 30s application of 10μmol/L ACh in SR patients was greater(12.8%, n=7-25)than in AF patients.Therefore,it is concluded that desensitization of cholinergic stimulation can be involved in atrial fibrillation.

【Keywords】

atrial fibrillation;;cholinergic stimulation;;desensitization;;muscarinic K~+ current

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