cGMP-Dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells

Guanosine-3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (cGMP-PK) plays a central role in the mediation of the vasodilator response to nitric oxide (NO) and other nitrovasodilators. It is unclear whether cGMP- PK affects calcium-activated potassium channels (K(Ca) channels) or any other type of ion channel in smooth muscle. We provide here the first direct evidence that cGMP-PK can activate K(Ca) channels in arterial smooth muscle cells. We demonstrate that NO and a membrane-permeable analogue of cGMP can activate K(Ca) channels in on-cell patches approximately twofold. Furthermore, cGMP-PK, in the presence of ATP and cGMP added directly to the intracellular surface of inside-out patches, increases channel activity by approximately eightfold. These results suggest that cGMP-PK-mediated activation of K(Ca) channels may contribute to the actions of NO and other nitrovasodilators.