Blockade of Adenosine Tripbospbate - sensitive Potassium channels by Zbiamylal in Rat Ventricular

Background: The adenosine triphosphate (ATPhensitive potassium (KAm) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATp channels in isolated rat ventricular myocytes during simulated ischemia. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATp channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of thiamylal(50 mg/l). Results: In the cell-attached configuration, 2,4-dinitrophenoI caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KAm channels. Open probability of KA1.,, channels was reduced by thiamylal in a concentration-dependent manner. KAm channels could be activated in the inside-out configuration because of the absence of AW. Thiamylal inhibited KKTP channel activity without changing the single-channel conductance. Conclusions: The result.. obtained in this study indicate that thiamylal inhibits KAm channel activities in cell-attached and