Differential role of epicardial and endocardial KATP channels in potassium accumulation during regional ischemia induced by embolization of a coronary artery with latex

Epicardial 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(+)](0)) might be 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-mu m late beads into the occluded artery to interrupt collateral flow, by which accumulated [K(+)](0) might wash out, Epicardial and endocardial [K(+)](0) 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(+)](0) among the three groups. In the control group, epicardial and endocardial [K(+)](0) were increased to a similar level as a function of time after occlusion (CTRL) at both layers. Ischemia-induced epicardial [K(+)](0) 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(+)](0) 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(+)](0) rise, but not in endocardial [K(+)](0) rise, during regional ischemia, Another mechanism(s) may be important for endocardial [K(+)](0) accumulation.