Blockade of myocardial ATP-sensitive potassium channels by ketamine

Background: The adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel underlies the increase in potassium permeability during hypoxia and ischemia. The increased outward potassium current during ischemia may be an endogenous cardioprotective mechanism. This study was designed to determine the effects of ketamine on K(ATP) channel in rat hearts. Methods: Inside-out and cell-attached configurations of patch-clamp techniques and 3 M potassium chloride-filled conventional microelectrodes were used to investigate the effect of ketamine on K(ATP) channel currents in single rat ventricular myocytes and on the action potential duration of rat papillary muscles, respectively. Results: Ketamine inhibited K(ATP) channel activity in rat ventricular myocytes in a concentration-dependent manner. In the inside- out patches, the concentration of ketamine for half-maximal inhibition and the Hill coefficient were 62.9 μM and 0.54, respectively. In a concentration-dependent manner, ketamine inhibited pinacidil- and 2,4- dinitrophenol-activated K(ATP) channels in cell-attached patches. The application of ketamine to the intracellular side of membrane patches did not affect the conduction of single-channel currents of K(ATP) channels. Ketamine increased the action potential duration, which was then shortened by pinacidil in a concentration-dependent manner. Conclusions: Ketamine inhibited K(ATP) channel activity in a concentration-dependent manner. These results suggest that ketamine may attenuate the cardioprotective effects of the K(ATP) channel during ischemia and reperfusion in the rat myocardium.