Unique Properties of the ATP-Sensitive K+ Channel in the Mouse Ventricular Cardiac Conduction System

Background-The specialized cardiac conduction system (CCS) expresses a unique complement of ion channels that confer a specific electrophysiological profile. ATP-sensitive potassium (K-ATP) channels in these myocytes have not been systemically investigated. Methods and Results-We recorded KATP channels in isolated CCS myocytes using Cntn2-EGFP reporter mice. The CCS KATP channels were less sensitive to inhibitory cytosolic ATP compared with ventricular channels and more strongly activated by MgADP. They also had a smaller slope conductance. The 2 types of channels had similar intraburst open and closed times, but the CCS KATP channel had a prolonged interburst closed time. CCS KATP channels were strongly activated by diazoxide and less by levcromakalim, whereas the ventricular KATP channel had a reverse pharmacological profile. CCS myocytes express elevated levels of Kir6.1 but reduced Kir6.2 and SUR2A mRNA compared with ventricular myocytes (SUR1 expression was negligible). SUR2B mRNA expression was higher in CCS myocytes relative to SUR2A. Canine Purkinje fibers expressed higher levels of Kir6.1 and SUR2B protein relative to the ventricle. Numeric simulation predicts a high sensitivity of the Purkinje action potential to changes in ATP: ADP ratio. Cardiac conduction time was prolonged by low-flow ischemia in isolated, perfused mouse hearts, which was prevented by glibenclamide. Conclusions-These data imply a differential electrophysiological response (and possible contribution to arrhythmias) of the ventricular CCS to KATP channel opening during periods of ischemia. (Circ Arrhythm Electrophysiol. 2011;4:926-935.)