Four novel splice variants of sulfonylurea receptor 1

ATP-sensitiveK⁺ (K_ATP) channels are composed of pore-formingKir6.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 pigSUR1. Three splice forms originate from alternative splicing of theregion coding for NBF1 and lack exons 17 (SUR117), 19 (SUR119),or both (SUR11719). The fourth (SUR1C) is a COOH-terminal SUR1-fragment formed by exons 31-39 containing the last twotransmembrane segments and the COOH terminus of SUR1. RT-PCR analysisshowed that these splice forms are expressed in several tissues with strong expression of SUR1C in cardiomyocytes. Confocal microscopy usingenhanced green fluorescent protein-tagged SUR or Kir6.x did not provideany evidence for involvement of these splice forms in themitochondrial K_ATP channel. Only SUR1 and SUR117 showed high-affinity binding of glibenclamide (K_d 2 nM in the presence of 1 mM ATP) and formed functional K_ATPchannels upon coexpression with Kir6.2.