Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BΔ31
L Gros, S Trapp, M Dabrowski… - British journal of …, 2002 - Wiley Online Library
British journal of pharmacology, 2002•Wiley Online Library
The ATP‐sensitive potassium channel (KATP) of pancreatic β‐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. 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 …
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. 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 …
- The ATP‐sensitive potassium channel (KATP) of pancreatic β‐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.
- 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 KATP channel.
- SUR1BΔ31, detected in several human tissues, is a splice variant of the rat SUR1 gene that lacks exon 31 of the corresponding human SUR1 gene. SUR1BΔ31 lacks the TM16–TM17 transmembrane‐spanning helices leading to a protein with a different transmembrane topology. Coinjection of SUR1BΔ31 plus Kir6.2 into Xenopus oocytes or expression of the Kir6.2/SUR1BΔ31 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.
- SUR1A2 and SUR1A1 proteins expressed in HEK‐293 cells display similar binding affinities for [3H]‐glibenclamide, while SUR1BΔ31 shows a 500‐fold lower affinity.
- These findings confirm that TM16–TM17 of SUR1 are important for high‐affinity glibenclamide binding and that their deletion impairs trafficking of the KATP channel to the surface membrane.
British Journal of Pharmacology (2002) 137, 98–106. doi:10.1038/sj.bjp.0704836
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