Low temperature completely rescues the function of two misfolded K ATP channel disease-mutants.
The pancreatic ATP-sensitive potassium channels comprise two subunits: SUR1 and Kir6.2. Two SUR1 mutations, A116P and V187D, reduce channel activity causing persistent hyperinsulinemic hypoglycemia of infancy. We investigated whether these mutations cause temperature sensitive misfolding. We show that the processing defect of these mutants is temperature sensitive and these two mutations disrupt the association between SUR1 and Kir6.2 by causing misfolding in SUR1 at 37 degrees C but can be rescued at 18 degrees C. Extensive electrophysiological characterization of these mutants indicated that low temperature largely, if not completely, corrects the folding defect of these two SUR1 mutants observed at 37 degrees C.
Yang
Ke
K
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Fang
Kun
K
Fromondi
Laura
L
Chan
Kim W
KW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D003080:Cold Temperature; D044903:Congenital Hyperinsulinism / Q000235:genetics*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D000255:Adenosine Triphosphate