K-ATP CHANNEL INHIBITION BY ATP REQUIRES DISTINCT FUNCTIONAL DOMAINS OF THE CYTOPLASMIC C-TERMINUS OF THE PORE-FORMING SUBUNIT

ATP-sensitive potassium (''K-ATP'') channels are rapidly inhibited bg intracellular ATP. This inhibition plays a crucial role in the couplin g of electrical activity to energy metabolism in a variety of cells. T he K-ATP channel is formed from four each of a sulfonylurea receptor ( SUR) regulatory subunit and an inwardly rectifying potassium (K(ir)6.2 ) pore-forming submit. We used systematic chimeric and point mutagenes is, combined with patch-clamp recording, to investigate the molecular basis of ATP-dependent inhibition gating of mouse pancreatic beta cell K-ATP channels expressed in Xenopus oocytes. We identified distinct f unctional domains of the presumed cytoplasmic C-terminal segment of th e K(ir)6.2 subunit that play an important role in this inhibition. Our results suggest that one domain is associated with inhibitory ATP bin ding and another with gate closure.