Differential Role of Epicardial and Endocardial K ATP Channels in Potassium Accumulation During Regional Ischemia Induced by Embolization of a Coronary Artery with Latex

Epicardial and and Endocardial [K + ] 0 Rise and K ATP Channels. Introduction : K ATP channels are activated predominantly in the epicardium during regional ischemia. Therefore, the role of K ATP channels in ischemia‐induced rise of extracellular potassium concentration ([K + ] o ) might he greater in the epicardium. Methods and Results : In 18 anesthetized dogs, the left anterior descending coronary artery (LAD) was ligated, followed by injection of 23‐μm latex heads into the occluded artery to interrupt collateral flow, by which accumulated [K + ] o might wash out. Epicardial and endocardial [K + ] o were measured during a 20‐minute period of ischemia using a valinomycin membrane. The dogs were divided into three groups: 6 control dogs (CTRL); 7 dogs pretreated with intravenous glibenclamide (0.3 mg/kg [GLIB]), a blocker of K ATP channels: and 5 dogs pretreated with intravenous nicorandil (0.2 to 0.25 mg/kg [NCR]), a K ATP channel opener. Before LAD occlusion, there was no difference in [K + ] o among the three groups. In the control group, epicardial and endocardial [K + ] o were increased to a similar level as a function of time after occlusion (CTRL) at both layers. Ischemia‐induced epicardial [K + ] o rise was suppressed by GLIB (8.4 ± 0.4 vs 6.7 ± 0.5 mM, P < 0.05) but augmented by NCR (12.9 ± 2.0 mM, P < 0.05). In contrast, endocardial [K + ] o , rise remained unaffected (7.6 ± 0.2 mM CTRL, 7.6 ± 1.3 mM GLIB, and 9.4 ± 2.2 mM NCR, P = NS). Conclusion : Activation of K ATP channels plays an important role in epicardial [K + ] o rise, but not in endocardial [K + ] o rise, during regional ischemia. Another mechanism(s) may he important for endocardial [K + ] o accumulation.