Activation of an ATP-dependent K+ conductance in Xenopus oocytes by expression of adenylate kinase cloned from renal proximal tubules

In rabbit proximal convoluted tubules, an ATP-sensitive K+ (K-ATP) channel has been shown to be involved in membrane cross-talk, i.e. the coupling (mo st likely mediated through intracellular ATP) between transepithelial Na+ t ransport and basolateral K+ conductance. This K+ conductance is inhibited b y taurine. We sought to isolate this K+ channel by expression cloning in Xe nopus oocytes. Injection of renal cor tex mRNA into oocytes induced a K+ co nductance, largely inhibited by extracellular Ba2+ and intracellular taurin e. Using this functional test, we isolated from our proximal tubule cDNA li brary a unique clone, which induced a large K+ current which was Ba2+-, tau rine- and glibenclamide-sensitive. Surprisingly, this clone is not a K+ cha nnel but an adenylate kinase protein (AK3), known to convert NTP+AMP into N DP+ADP (N could be G, I or A). AK3 expression resulted in a large ATP decre ase and activation of the whole-cell currents including a previously unknow n, endogenous K+ current. To verify whether ATP decrease was responsible fo r the current activation, we demonstrated that inhibition of glycolysis gre atly reduces oocyte ATP levels and increases an inwardly rectifying K+ curr ent. The possible involvement of AK in the K-ATP channel's regulation provi des a means of explaining their observed activity in cytosolic environments characterized by high ATP concentrations. (C) 2001 Elsevier Science B.V. A ll rights reserved.