Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 10, Pages 8793-8799Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M413426200
Keywords
-
Categories
Ask authors/readers for more resources
Zinc at micromolar concentrations hyperpolarizes rat pancreatic beta-cells and brain nerve terminals by activating ATP-sensitive potassium channels (K-ATP). The molecular determinants of this effect were analyzed using insulinoma cell lines and cells transfected with either wild type or mutated K-ATP subunits. Zinc activated K-ATP in cells coexpressing rat Kir6.2 and SUR1 subunits, as in insulinoma cell lines. In contrast, zinc exerted an inhibitory action on SUR2A-containing cells. Therefore, SUR1 expression is required for the activating action of zinc, which also depended on extracellular pH and was blocked by diethyl pyrocarbonate, suggesting histidine involvement. The five SUR1-specific extracellular histidine residues were submitted to site-directed mutagenesis. Of them, two histidines (His-326 and His-332) were found to be critical for the activation of K-ATP by zinc, as confirmed by the double mutation H326A/H332A. In conclusion, zinc activates K-ATP by binding itself to extracellular His-326 and His-332 of the SUR1 subunit. Thereby zinc could exert a negative control on cell excitability and secretion process of pancreatic beta-and alpha-cells. In fact, we have recently shown that such a mechanism occurs in hippocampal mossy fibers, a brain region characterized, like the pancreas, by an important accumulation of zinc and a high density of SUR1-containing K-ATP.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available