Four novel splice variants of sulfonylurea receptor 1.

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Hambrock A, Preisig-Muller R, Russ U, Piehl A, Hanley PJ, Ray J, Daut J, Quast U, Derst C

Four novel splice variants of sulfonylurea receptor 1.

Am J Physiol Cell Physiol. 2002 Aug;283(2):C587-98.

PubMed ID

12107069 [ View in PubMed

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Abstract

ATP-sensitive K(+) (K(ATP)) channels are composed of pore-forming Kir6.x subunits and regulatory sulfonylurea receptor (SUR) subunits. SURs are ATP-binding cassette proteins with two nucleotide-binding folds (NBFs) and binding sites for sulfonylureas, like glibenclamide, and for channel openers. Here we report the identification and functional characterization of four novel splice forms of guinea pig SUR1. Three splice forms originate from alternative splicing of the region coding for NBF1 and lack exons 17 (SUR1Delta17), 19 (SUR1Delta19), or both (SUR1Delta17Delta19). The fourth (SUR1C) is a COOH-terminal SUR1-fragment formed by exons 31-39 containing the last two transmembrane segments and the COOH terminus of SUR1. RT-PCR analysis showed that these splice forms are expressed in several tissues with strong expression of SUR1C in cardiomyocytes. Confocal microscopy using enhanced green fluorescent protein-tagged SUR or Kir6.x did not provide any evidence for involvement of these splice forms in the mitochondrial K(ATP) channel. Only SUR1 and SUR1Delta17 showed high-affinity binding of glibenclamide (K(d) approximately 2 nM in the presence of 1 mM ATP) and formed functional K(ATP) channels upon coexpression with Kir6.2.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glyburide	Sulfonylurea receptor 1, Kir6.2 (Protein Group)	Protein group	Humans	Yes	Blocker	Details
Glymidine	ATP-binding cassette sub-family C member 8	Protein	Humans	Unknown	Inducer	Details