RGD Reference Report - Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. - Rat Genome Database

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Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31.

Authors: Gros, L  Trapp, S  Dabrowski, M  Ashcroft, FM  Bataille, D  Blache, P 
Citation: Gros L, etal., Br J Pharmacol 2002 Sep;137(1):98-106.
RGD ID: 728122
Pubmed: PMID:12183335   (View Abstract at PubMed)
PMCID: PMC1573464   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.bjp.0704836   (Journal Full-text)

1. The ATP-sensitive potassium channel (K(ATP)) of pancreatic beta-cells is composed of the sulphonylurea-binding protein, SUR1, and the inwardly rectifying K(+) channel subunit, Kir6.2. We have characterized two novel isoforms of rat SUR1 in the RINm5F insulin-secreting cell line. 2. SUR1A2 is an allelic variant with a single amino acid change in the first nucleotide-binding domain. Coinjection of SUR1A2 plus Kir6.2 into Xenopus oocytes or expression of a SUR1A2-Kir6.2 tandem in HEK-293 cells yielded large currents with characteristics similar to the wild-type K(ATP) channel. 3. SUR1BDelta31, detected in several human tissues, is a splice variant of the rat SUR1 gene that lacks exon 31 of the corresponding human SUR1 gene. SUR1BDelta31 lacks the TM16-TM17 transmembrane-spanning helices leading to a protein with a different transmembrane topology. Coinjection of SUR1BDelta31 plus Kir6.2 into Xenopus oocytes or expression of the Kir6.2/SUR1BDelta31 tandem construct in HEK-293 cells did not result in any current, and a surface expression assay indicated that this channel does not reach the plasma membrane. 4. SUR1A2 and SUR1A1 proteins expressed in HEK-293 cells display similar binding affinities for [(3)H]-glibenclamide, while SUR1BDelta31 shows a 500-fold lower affinity. 5. These findings confirm that TM16-TM17 of SUR1 are important for high-affinity glibenclamide binding and that their deletion impairs trafficking of the K(ATP) channel to the surface membrane.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of voltage-gated potassium channel activity  IMP 728122 RGD 

Objects Annotated

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


Additional Information