Protein kinase C-independent inhibition of the Ca(2+)-activated K+ channel by angiotensin II and endothelin-1.
We previously reported that the Ca(2+)-activated K+ channel (KCa-channel) in cultured smooth muscle cells from porcine coronary artery was inhibited by protein kinase C (C-kinase). In this study, inhibition of the KCa-channel by receptor-mediated vascular contractile agonists, such as angiotensin II (ANG II) and endothelin-1 (ET-1), was investigated by the patch-clamp technique. In cell-attached patches, addition of ANG II (500 nM) or ET-1 (50 nM) to the bath inhibited the KCa-channel activated by the calcium ionophore A23187 (10-20 microM). Phorbol 12-myristate 13-acetate (PMA, 1 microM), a C-kinase activator, also decreased the open probability of the KCa-channel. The PMA-induced decrease in the open probability was reversed by subsequent application of staurosporine (1 nM), a C-kinase inhibitor, but the ANG II- and ET-1-induced decreases were not reversed by subsequent application of staurosporine (> 30 nM). Pretreatment of smooth muscle cells with 30 nM staurosporine, a protein kinase inhibitor, or 1 mM neomycin, an inhibitor of phospholipase C, also did not abolish the inhibition of the KCa-channel by ANG II. Furthermore, ANG II inhibited the KCa-channel in cells in which C-kinase was down-regulated. These results indicate that, in porcine coronary artery smooth muscle cells, ANG II and ET-1 inhibit the KCa-channel by a C-kinase-independent mechanism.
Minami
K
K
Laboratory of Health Chemistry, Faculty of Pharmaceutical Sciences, Tokushima University, Japan.
Hirata
Y
Y
Tokumura
A
A
Nakaya
Y
Y
Fukuzawa
K
K
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D016232:Endothelins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D000804:Angiotensin II; D000001:Calcimycin; D011493:Protein Kinase C; D019311:Staurosporine; D009355:Neomycin; D013755:Tetradecanoylphorbol Acetate