PHARMACOLOGY OF ATP-SENSITIVE K-MUSCLE CELLS FROM RABBIT MESENTERIC-ARTERY( CURRENTS IN SMOOTH)

The inference that ATP-sensitive K+ (K-ATP) channels are involved in a rterial responses to the synthetic K+ channel openers, hypoxia, adenos ine, and calcitonin gene-related peptide, has relied on the sensitivit y of these responses to the sulfonylureas glibenclamide and tolbutamid e 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 mu M), cromakalim (half-activation 1.9 mu M), an d diazoxide (half-activation 37.1 mu M) activated K+-selective current s that were blocked by glibenclamide. Elevation of pipette (intracellu lar) ATP concentration decreased K+ currents induced by pinacidil. Hal f-inhibition of K-ATP currents by glibenclamide and tolbutamide occurr ed at 101 nM and 351 mu M, respectively. K-ATP currents were also inhi bited by external TEA(+), with half-inhibition at 6.2 mM. The results indicate that glibenclamide is an effective inhibitor of K-ATP channel s in arterial smooth muscle and that tolbutamide and TEA(+) are much l ess effective. Furthermore, these results support numerous functional studies that have demonstrated that the vasorelaxations to K+ channel openers are inhibited by < 10 mu M glibenclamide but not by < 1 mM TEA (+).