Role Of Pacemaker Current In The Occurrence Of Paroxysmal Atrial Fibrillation In The Elderly And It's Molecular Mechanism

Atrial fibrillation is the most common persistent arrhythmia in clinic,and it's incident increases with age.According to the research results,90%paroxysmal atrial fibrillation(PAF) originate in pulmonary vein sleeve(PVs).As an important mechanism for the trigger of atrial fibrillation,rise of pulmonary vein sleeve automaticity plays an irreplaceable role in the occurence and maintenance of PAF.The aim of the present study is to investigate the characteristics of ectopic automaticity and I_f of cardiomyocytes from pulmonary veins in older canine with atrial fibrillation.The older canines(7-9 years) were subjected to long-term rapidly atrial pacing for 10 weeks,which induced atrial fibrillation models. Disassociation of PVs of canines yielded single cardiomyocytes from a Landengorff column.I_f current was measured with the patch-clamp technique. Compared with the control group,cardiomyocytes from the rapidly atrial pacing canine PVs had spontaneous diastolic depolarization,shorter action potential duration,and larger I_f densities.Furthermore,I_f currents in the RAP were reduced by Ivabradine,a selective inhibitor of the I_f current.As contrast,I_f current densities were increased significantly by beta-adrenergic receptor stimulation with isoproterenol.Either mRNA or protein expression of HCN4 in cardiomyocytes from PVs in older canine is larger than that of HCN2.Our study revealed an increased I_f in the PVs from older canines with atrial fibrillation. Our results suggested that I_f of PVs with RAP contributed partly to ectopy in atrial fibrillation.