Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery

The inference that ATP-sensitive K+ (K(ATP)) channels are involved in arterial responses to the synthetic K+ channel openers, hypoxia, adenosine, and calcitonin gene-related peptide, has relied on the sensitivity of these responses to the sulfonylureas glibenclamide and tolbutamide and to tetraethylammonium (TEA+). The inhibition of K(ATP), currents by glibenclamide, tolbutamide, and TEA+ was investigated in single smooth muscle cells from rabbit mesenteric artery by use of the whole cell patch- clamp technique. The synthetic K+ channel openers pinacidil (half- activation 0.6 μM), cromakalim (half-activation 1.9 μM), and diazoxide (half-activation 37.1 μM) activated K+-selective currents that were blocked by glibenclamide. Elevation of pipette (intracellular) ATP concentration decreased K+ currents induced by pinacidil. Half-inhibition of K(ATP) currents by glibenclamide and tolbutamide occurred at 101 nM and 351 μM, respectively. K(ATP) currents were also inhibited by external TEA+, with half-inhibition at 6.2 mM. The results indicate that glibenclamide is an effective inhibitor of K(ATP) channels in arterial smooth muscle and that tolbutamide and TEA+ are much less effective. Furthermore, these results support numerous functional studies that have demonstrated that the vasorelaxations to K+ channel openers are inhibited by <10 μM glibenclamide but not by <1 mM TEA+.