Neonatal diabetes caused by mutations in sulfonylurea receptor 1: interplay between expression and Mg-nucleotide gating defects of ATP-sensitive potassium channels.

ABSTRACT:

Context

ATP-sensitive potassium (KATP) channels regulate insulin secretion by coupling glucose metabolism to β-cell membrane potential. Gain-of-function mutations in the sulfonylurea receptor 1 (SUR1) or Kir6.2 channel subunit underlie neonatal diabetes.

Objective

The objective of the study was to determine the mechanisms by which two SUR1 mutations, E208K and V324M, associated with transient neonatal diabetes affect KATP channel function.

Design

E208K or V324M mutant SUR1 was coexpressed with Kir6.2 in COS cells, and expression and gating properties of the resulting channels were assessed biochemically and electrophysiologically.

Results

Both E208K and V324M augment channel response to MgADP stimulation without altering sensitivity to ATP4- or sulfonylureas. S

SUBMITTER: Zhou Q 

PROVIDER: S-EPMC2999977 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature