REGIONAL LOCALIZATION OF ERG, THE CHANNEL PROTEIN RESPONSIBLE FOR THERAPID COMPONENT OF THE DELAYED RECTIFIER, K+ CURRENT IN THE FERRET HEART

Repolarization of the cardiac action potential varies widely throughou t the heart. This could be due to the differential distribution of ion channels responsible for repolarization, especially the K+ channels. We have therefore studied the cardiac localization of ERG, a channel p rotein known to play an important role in generation of the rapid comp onent of the delayed rectifier K+ current (I-Kr), an important determi nant of the repolarization waveform. Cryosections of the ferret atrium and ventricle were prepared to determine the localization of ERG by f luorescence in situ hybridization (FISH) and immunofluorescence. We fo und that in the ferret, ERG transcript and protein expression was most abundant in the epicardial cell layers throughout most of the ventric le, except at the base. In the atrium, we found that ERG is most abund ant in the medial right atrium, especially in the trabeculae and the c rista terminalis of the right atrial appendage. It also is present in areas within the sinoatrial node. In all regions studied, FISH and imm unofluorescence showed concordant localization patterns. These data su ggest that repolarization mediated by I, is not uniform throughout the ferret heart and provide a molecular explanation for heterogeneity in action potential repolarization throughout the mammalian heart.