Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BΔ31

The ATP‐sensitive potassium channel (K ATP ) 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 K ATP 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 [ 3 H]‐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 K ATP channel to the surface membrane.British Journal of Pharmacology (2002) 137 , 98–106. doi: 10.1038/sj.bjp.0704836