Pharmacology and modulation of KATP 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.