Dual action of endothelin-1 on the Ca2(+)-activated K+ channel in smooth muscle cells of porcine coronary artery.
The effects of endothelin-1 (ET-1) on the activity of the large Ca2(+)-activated K+ channel (BK channel) in enzymatically dissociated smooth muscle cells of porcine coronary artery were studied with the cell-attached patch-clamp technique. ET-1 at concentrations between 0.1 and 10 nM potentiated the BK channel activity. This effect was maximal at 1 nM ET-1, resulting in an average of 4.2-fold increase in channel open-state probability as compared with control. ET-1 at concentrations higher than 10 nM produced an irreversible inhibition of the BK channel activity, primarily due to a marked decrease in the channel mean open-time. The activation by lower doses of ET-1, but not the inhibition by higher doses of ET-1, of the BK channel was blocked by 0.1 microM PN 200-110, a Ca2+ channel blocker. The modulation of the BK channel activity in smooth muscle cell membrane may be a possible mechanism for ET-induced vasodilator and vasoconstrictor actions.
Hu
S L
SL
Research Department, Ciba-Geigy Corp., Summit, NJ 07901.
Kim
H S
HS
Jeng
A Y
AY
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D017275:Isradipine; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013552:Swine
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016232:Endothelins; D010069:Oxadiazoles; D015221:Potassium Channels; D017275:Isradipine