ATP INCREASES CA2-ACTIVATED K+ CHANNEL ACTIVITY IN ISOLATED RAT ARTERIAL SMOOTH-MUSCLE CELLS()

Large conductance Ca2+-activated K+(K-Ca) channels are known to be act ivated by phosphorylation through cAMP- and cGMP-dependent kinase acti vation, In pulmonary arterial smooth muscle K-Ca channels are directly activated by ATP (but not by non-hydrolysable analogues) independentl y of the presence of cyclic nucleotides or the catalytic subunits of p rotein kinases. This study was designed to determine whether direct ac tivation of K-Ca channels by ATP is apparent in other types of arteria l smooth muscle. K-Ca channels of similar conductance to those of rat pulmonary artery (approximate to 250 pS) were found in membrane patche s excised from isolated smooth muscle cells from rat aorta. mesenteric and basilar arteries, In myocytes isolated from each of these arterie s, intracellular application of ATP (in the absence of exogenous cycli c nucleotides or catalytic subunits) reversibly increased the open sta te probability of K-Ca channels: a response markedly reduced by a spec ific inhibitor of protein kinase A. Nucleotide sequence analysis of K- Ca channels revealed no homology with the majority of protein kinases. It is concluded that phosphorylation of K-Ca channels through the act ivity of a membrane tethered kinase related to protein kinase A (but l acking its regulatory subunits) may play an important role in controll ing K+ flux in a range of arterial smooth muscle cell types.