Heterogeneity and function of KATP channels in canine hearts

BackgroundThe concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (KATP) channels is challenged by recent reports that SUR1 is predominant in mouse atrial KATP channels.ObjectiveTo assess SUR subunit composition of KATP channels and consequence of KATP activation for action potential duration (APD) in dog hearts.MethodsPatch-clamp techniques were used on isolated dog cardiomyocytes to investigate KATP channel properties. Dynamic current clamp, by injection of a linear K+ conductance to simulate activation of the native current, was used to study the consequences of KATP activation on APD.ResultsMetabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean KATP conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected KATP current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes.ConclusionsEven a small fraction of KATP activation significantly shortens APD in a manner that depends on existing heterogeneity in KATP current and APD.