FUNCTIONAL COMMUNICATION BETWEEN CARDIAC ATP-SENSITIVE K+ CHANNEL ANDNA K ATPASE/

Introduction: Functional interaction between K-ATP channel and Na/K AT Pase was studied in single guinea pig ventricular myocytes because bot h membrane molecules are known to be involved in ischemic episodes. Me thods and Results: K-ATP channel currents were recorded at 36 degrees C by using whole cell, cell-attached, inside-out, and open cell-attach ed modes of patch clamp techniques on enzymatically isolated ventricul ar myocytes, In the whole cell mode, ouabain (1 mu M) reversibly inhib ited the K-ATP currents induced by metabolic stress (ATP-free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100 mu M), a K-ATP channel opener. In the cell-attached mode, ouabain concen tration dependently inhibited K-ATP channel opening induced by metabol ic: suppression (5.5 mM 2-deoxyglucose and 1 mM CN-), Half-inhibition concentration for ouabain was 21.0 +/- 5.5 nM and the Hill coefficient was 0.8 +/- 0.1 (n = 26), However, ouabain did not have an effect on the channel activity induced by cromakalim (100 mu M) In the inside-ou t mode, ouabain applied to the internal side of membrane did not affec t the channel. In the open cell-attached mode made by preincubation wi th streptolysin-O (0.08 U/mL), the K-ATP channels were not activated b y the metabolic inhibitors but were by reducing extracellular ATP conc entrations, because subsarcolemmal ATP concentration could be controll ed through tiny membrane holes. The channels thus activated were not s uppressed by ouabain, Conclusion: The inhibition of Na/K ATPase by oua bain appeared to block the K-ATP channels by accumulating subsarcolemm al ATP caused by a decrease of the transition from ATP to ADP, In the presence of ischemic episodes, the administration of digitalis compoun ds may affect the opening of K-ATP channels, which is primarily protec tive against the development of irreversible myocardial damage.