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Low temperature completely rescues the function of two misfolded K ATP channel disease‐mutants
Author(s) -
Yang Ke,
Fang Kun,
Fromondi Laura,
Chan Kim W.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.06.039
Subject(s) - mutant , kir6.2 , hyperinsulinemic hypoglycemia , potassium channel , mutation , sulfonylurea receptor , folding (dsp implementation) , chemistry , electrophysiology , protein subunit , microbiology and biotechnology , biophysics , biology , biochemistry , endocrinology , hypoglycemia , neuroscience , gene , insulin , engineering , electrical engineering
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 °C but can be rescued at 18 °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 °C.