RGD Reference Report - Two SUR1-specific histidine residues mandatory for zinc-induced activation of the rat KATP channel. - Rat Genome Database

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Two SUR1-specific histidine residues mandatory for zinc-induced activation of the rat KATP channel.

Authors: Bancila, V  Cens, T  Monnier, D  Chanson, F  Faure, C  Dunant, Y  Bloc, A 
Citation: Bancila V, etal., J Biol Chem. 2005 Mar 11;280(10):8793-9. Epub 2004 Dec 21.
RGD ID: 1598638
Pubmed: PMID:15613469   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M413426200   (Journal Full-text)

Zinc at micromolar concentrations hyperpolarizes rat pancreatic beta-cells and brain nerve terminals by activating ATP-sensitive potassium channels (KATP). The molecular determinants of this effect were analyzed using insulinoma cell lines and cells transfected with either wild type or mutated KATP subunits. Zinc activated KATP in cells co-expressing 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 KATP by zinc, as confirmed by the double mutation H326A/H332A. In conclusion, zinc activates KATP 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 KATP.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to pH  IDA 1598638 RGD 
response to zinc ion  IDA 1598638 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)


Additional Information