ATP-SENSITIVE K-ARTERY( CHANNELS MEDIATE VASODILATION PRODUCED BY LEMAKALIM IN RABBIT PULMONARY)

Tension recording and the patch-clamp technique were used to determine the mechanism underlying vasodilation produced by lemakalim in the ra bbit pulmonary artery. Lemakalim produced relaxation of precontracted muscle strips that was inhibited by glibenclamide and tetrapentylammon ium ions but not by 2 mM tetraethylammonium (TEA) ions. In single cell s dialyzed with 1 mM ATP, lemakalim (10 muM) hyperpolarized cells by a pproximately 13 mV and activated a time-independent K+ current, averag ing only 6.5 pA at -50 mV. Glibenclamide reversed both of these membra ne effects of lemakalim but not the lemakalim-induced block of an outw ard current seen above -20 mV. ATP depletion hyperpolarized cells and selectively unmasked a background K+ current, which was sensitive to g libenclamide but not to TEA, with properties similar to the current ac tivated by lemakalim during membrane hyperpolarization. Furthermore, w hen intracellular ATP concentrations were varied, a clear correlation was revealed between ATP levels and the magnitude of the depolarizatio n or hyperpolarization seen with either glibenclamide or lemakalim, re spectively. These results provide direct evidence that the background current is carried by ATP-sensitive K+ channels rather than by large-c onductance Ca2+-activated K+ channels and that it underlies the hyperp olarization and relaxation to lemakalim.