Pharmacology and modulation of K(ATP) channels by protein kinase C and phosphatases in gallbladder smooth muscle.
ATP-sensitive K(+) (K(ATP)) channels exhibit pharmacological diversity, which is critical for the development of novel therapeutic agents. We have characterized K(ATP) channels in gallbladder smooth muscle to determine how their pharmacological properties compare to K(ATP) channels in other types of smooth muscle. K(ATP) currents were measured in myocytes isolated from gallbladder and mesenteric artery. The potencies of pinacidil, diazoxide, and glibenclamide were similar in gallbladder and vascular smooth muscle, suggesting that the regions of the channel conferring sensitivity to these agents are conserved among smooth muscle types. Activators of protein kinase C (PKC), however, were less effective at inhibiting K(ATP) currents in myocytes from gallbladder than mesenteric artery. The phosphatase inhibitor okadaic acid increased the efficacy of PKC activators and revealed ongoing basal activation of K(ATP) channels by protein kinase A in gallbladder. These results suggest that phosphatases and basal kinase activity play an important role in controlling K(ATP) channel activity.
Firth
T A
TA
Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
Mawe
G M
GM
Nelson
M T
MT
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D019319:Okadaic Acid; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D003981:Diazoxide; D005905:Glyburide