Differential role of sarcolemmal and mitochondrial K-ATP channels in adenosine-enhanced ischemic preconditioning

Adenosine-enhanced ischemic preconditioning (APC) extends the protection af forded by ischemic preconditioning (IPC) by both significantly decreasing i nfarct size and significantly enhancing postischemic functional recovery. T he purpose of this study was to determine whether APC is modulated by ATP-s ensitive potassium (K-ATP) channels and to determine whether this modulatio n occurs before ischemia or during reperfusion. The role of KATP channels b efore ischemia (I), during reperfusion (R), or during ischemia and reperfus ion (IR) was investigated using the nonspecific K-ATP blocker glibenclamide (Glb), the mitochondrial (mito) K-ATP channel blocker 5-hydroxydecanoate ( 5-HD), and the sarcolemmal (sarc) KATP channel blocker HMR-1883 (HMR). Infa rct size was significantly increased (P < 0.05) in APC hearts with Glb-I, G lb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treat ment significantly decreased APC functional recovery (P, 0.05 vs. APC), whe reas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR sig nificantly decreased postischemic functional recovery (P, 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size r eduction is modulated by mitoK(ATP) channels primarily during ischemia and suggest that functional recovery is modulated by sarcK(ATP) channels during ischemia and reperfusion.