ATP-SENSITIVE AND INWARDLY RECTIFYING POTASSIUM CHANNELS IN SMOOTH-MUSCLE

The properties and roles of ATP-sensitive (K-ATP) and inwardly rectify ing (K-IR) potassium channels are reviewed. Potassium channels regulat e the membrane potential of smooth muscle, which controls calcium entr y through voltage-dependent calcium channels, and thereby contractilit y through changes in intracellular calcium. The K-ATP channel is likel y to be composed of members of the inward rectifier channel gene famil y (Kir6) and sulfonylurea receptor proteins. The K-IR channels do not appear to be as widely distributed as K-ATP channels in smooth muscle and may provide a mechanism by which changes in extracellular K+ can a lter smooth muscle membrane potential, and thereby arterial diameter. The K-ATP channels contribute to the resting membrane conductance of s ome types of smooth muscle and can open under situations of metabolic compromise. The K-ATP channels are targets of a wide variety of vasodi lators and constrictors, which act, respectively, through adenosine 3' ,5'-cyclic monophosphate/protein kinase A and protein kinase C. The K- ATP channels are also activated by a number of synthetic vasodilators (e.g., diazoxide and pinacidil) and are inhibited by the oral hypoglyc emic sulfonylurea drugs (e.g., glibenclamide). Together, K-ATP, and K- IR channels are important regulators of smooth muscle function and rep resent important therapeutic targets.