K channel openers activate different K channels in vascular smooth muscle cells

Abstract

The properties of K channels activated by K channel openers (nicorandil, cromakalim, pinacidil, etc.) were investigated using conventional microelectrode and patch-clamp methods. In single smooth muscle cells of the rat and rabbit portal veins, K channel openers produced an outward current sensitive to glibenclamide, 4-AP, and TEA (1 mM), but insensitive to apamin and charybdotoxin. Glibenclamide-sensitive K channels in both tissues had a small unitary conductance (10 pS and 15 pS) and were inhibited by intracellular ATP. The activity of the 15 pS channel in the rabbit portal vein was not changed by an increase in the intracellular free Ca concentration, but the activity of the 10 pS channel in the rat portal vein was markedly modified by Ca concentration. These results coincided with previous observations using a conventional microelectrode and whole-cell voltage-clamp experiments. In the inside-out membrane patch, the 10 pS channel in the rat portal vein was activated by the application of K channel openers, while the 15 pS channel in the rabbit portal vein was rapidly inactivated, even in the presence of K channel openers. GDP, but neither GTP gamma S nor GDP beta S, reopened the 15 pS channel in the presence of K channel openers. These results suggested that the 15 pS channel had two channel states, that is, both operative and inoperative states, while the 10 pS channel did not have an inoperative state. The K channel openers open the ATP-sensitive K channel only at the operative state.(ABSTRACT TRUNCATED AT 250 WORDS)