Heterogeneity and function of K_ATP channels in canine hearts

Background The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K_ATP) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K _ATP channels. Objective To assess SUR subunit composition of K _ATP channels and consequence of K_ATP activation for action potential duration (APD) in dog hearts. Methods Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate K_ATP 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 K_ATP activation on APD. Results Metabolic 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 K_ATP 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 K_ATP current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes. Conclusions Even a small fraction of K_ATP activation significantly shortens APD in a manner that depends on existing heterogeneity in K_ATP current and APD.