MgATP activates the β cell K ATP channel by interaction with its SUR1 subunit

• DOI: 10.1073/pnas.95.12.7185
• Publication Date: 2002-07-26T14:42:40Z
• Authors: Fiona M. Gribble; Stephen J. Tucker; Trude Haug; Frances M. Ashcroft
• Keywords: Sulfonylurea receptor; Adenosine triphosphate; ATP-sensitive potassium channel

ATP-sensitive potassium (K ATP ) channels in the pancreatic β cell membrane mediate insulin release response to elevation of plasma glucose levels. They are open at rest but close metabolism, producing a depolarization that stimulates Ca 2+ influx and exocytosis. Metabolic regulation K channel activity currently is believed be mediated by changes intracellular concentrations MgADP, which inhibit activate channel, respectively. The complex four Kir6.2 pore-forming subunits SUR1 regulatory subunits: mediates inhibition ATP, whereas potentiatory action MgADP involves nucleotide-binding domains (NBDs) SUR1. We show here MgATP (like MgADP) able stimulate activity, this effect normally masked potent inhibitory nucleotide. Mg caused an apparent reduction on wild-type channels, actually activated containing mutation subunit impairs nucleotide (R50G). Both these effects were abolished when mutations made NBDs predicted abolish binding and/or hydrolysis (D853N, D1505N, K719A, or K1384M). These results suggest that, like interaction with Further support for idea sensitivity truncated form Kir6.2, shows functional expression absence SUR1, unaffected .