Properties and pharmacological modification of ATP-sensitive K+ channels in cat tracheal myocytes

1 The effects of leveromakalim and nucleoside diphosphates (NDPs) on both membrane currents and unitary currents in cat trachea myocytes were investigated by use of patch-clamp techniques. 2 In conventional whole-cell configuration, leveromakalim produced a concentration-dependent K+ current which was suppressed by additional application of 5 mu M glibenclamide at -70 mV. When 3 mM ATP was added in the pipette solution, the peak amplitude of the leveromakalim-induced current was much smaller than that in the absence of ATP. 3 When 3 mM uridine 5'-diphosphate (UDP) was included in the pipette solution, much higher concentrations of glibendamide (greater than or equal to 50 mu M) were required to suppress the 100 mu M leveromakalim-induced membrane current in comparison with those in the absence of UDP. 4 In the cell-attached patches, leveromakalim activated a 40 pS K+ channel which was inhibited by additional application of glibenclamide in symmetrical 140 mM K+ conditions. 5 UDP (greater than or equal to 0.1 mM) was capable of reactivating the channel in inside-out patches in which the glibenclamide-sensitive K+ channel had run down, in the presence of leveromakalim. The K+ channel reactivated by UDP was suppressed by additional application of either intracellular 3 mM ATP or 100 mu M glibenclamide. 6 These results demonstrate that smooth muscle cells in the cat trachea possess ATP-sensitive 40 pS K+ channels which are blocked by glibenclamide (i.e. K-ATP) and can be activated by leveromakalim and that intracellular UDP causes a significant shift of the glibenclamide-sensitivity of these channels.