Pharmacology and modulation of K(ATP) channels by protein kinase C and phosphatases in gallbladder smooth muscle

ATP-sensitiveK⁺ (K_ATP) channels exhibit pharmacologicaldiversity, which is critical for the development of novel therapeutic agents. We have characterized K_ATP channels in gallbladdersmooth 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 fromgallbladder and mesenteric artery. The potencies of pinacidil,diazoxide, and glibenclamide were similar in gallbladder and vascularsmooth muscle, suggesting that the regions of the channel conferringsensitivity to these agents are conserved among smooth muscle types.Activators of protein kinase C (PKC), however, were less effective atinhibiting K_ATP currents in myocytes from gallbladder thanmesenteric artery. The phosphatase inhibitor okadaic acid increased theefficacy of PKC activators and revealed ongoing basal activation ofK_ATP channels by protein kinase A in gallbladder. Theseresults suggest that phosphatases and basal kinase activity play animportant role in controlling K_ATP channel activity.