CLONING AND FUNCTIONAL-CHARACTERIZATION OF A NOVEL ATP-SENSITIVE POTASSIUM CHANNEL UBIQUITOUSLY EXPRESSED IN RAT-TISSUES, INCLUDING PANCREATIC-ISLETS, PITUITARY, SKELETAL-MUSCLE, AND HEART

ATP-sensitive K+ (K-ATP) channels play a crucial role in coupling metabolic energy to the membrane potential of cells. We have isolated a cDNA encoding a novel member (uK(ATP)-1) of the inward rectifier K+ channel family from a rat pancreatic islet cDNA library, Rat uK(ATP)-1 is a 424-amino acid residue protein (M(r) = 47,960), Electrophysiological studies of uK(ATP)-1 expressed in Xenopus laevis oocytes show that uK(ATP)-1 is a weak rectifier and is blocked with Ba2+ ions, Single-channel patch clamp study of clonal human kidney epithelial cells (HEK293) transfected with uK(ATP)-1 cDNA reveals that uK(ATP)-1 closes in response to 1 mM ATP and has a single channel conductance of 70 +/- 2 picosiemens (n = 6), indicating that uK(ATP)-1 is an ATP-sensitive inward rectifier K+ channel. In addition, uK(ATP)-1 is activated by the K-ATP channel opener, diazoxide. RNA blot analysis shows that uK(ATP)-1 mRNA is expressed ubiquitously in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart, suggesting that uK(ATP)-1 may play a physiological role as a link between the metabolic state and membrane K+ permeability of cells in almost every normal tissue. Since uK(ATP)-1 shares only 43-46% amino acid identity with members of previously reported inward rectifier K+ channel subfamilies, including ROMK1, IRK1, GIRK1, and cK(ATP)-1, uK(ATP)-1 is not an isoform of these subfamilies and, therefore, represents a new subfamily of the inward rectifier K+ channel family having two transmembrane segments.