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 (KCa channels) or any other type of ion channel in smooth muscle. We provide here the first direct evidence that cGMP-PK can activate KCa channels in arterial smooth muscle cells. We demonstrate that NO and a membrane-permeable analogue of cGMP can activate KCa 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 KCa channels may contribute to the actions of NO and other nitrovasodilators.
Robertson
B E
BE
Department of Pharmacology, University of Vermont Medical Research Facility, Colchester 05446.
Schubert
R
R
Hescheler
J
J
Nelson
M T
MT
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011494:Protein Kinases / Q000494:pharmacology*; D011817:Rabbits
D015221:Potassium Channels; D009569:Nitric Oxide; D011494:Protein Kinases; D002118:Calcium