ATP increases Ca(2+)-activated K+ channel activity in isolated rat arterial smooth muscle cells

Large conductance Ca(2+)-activated K+ (Kca) channels are known to be activated by phosphorylation through cAMP- and cGMP-dependent kinase activation. In pulmonary arterial smooth muscle KCa channels are directly activated by ATP (but not by non-hydrolysable analogues) independently of the presence of cyclic nucleotides or the catalytic subunits of protein kinases. This study was designed to determine whether direct activation of KCa channels by ATP is apparent in other types of arterial smooth muscle. KCa channels of similar conductance to those of rat pulmonary artery (approximately 250 pS) were found in membrane patches excised from isolated smooth muscle cells from rat aorta, mesenteric and basilar arteries. In myocytes isolated from each of these arteries, intracellular application of ATP (in the absence of exogenous cyclic nucleotides or catalytic subunits) reversibly increased the open state probability of KCa channels: a response markedly reduced by a specific inhibitor of protein kinase A. Nucleotide sequence analysis of KCa channels revealed no homology with the majority of protein kinases. It is concluded that phosphorylation of KCa channels through the activity of a membrane tethered kinase related to protein kinase A (but lacking its regulatory subunits) may play an important role in controlling K+ flux in a range of arterial smooth muscle cell types.