Alternative splicing of sur2 exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel

ATP-sensitive potassium channels (K-ATP) are implicated in a diverse array of physiological functions. Previous work has shown that alternative usage of exons 14, 39, and 40 of the muscle-specific K-ATP channel regulatory sub unit,, sur2, occurs in tissue-specific patterns. Here, we show that exon 17 of the first nucleotide binding fold of sur2 is also alternatively spliced . RNase protection demonstrates that SUR2(Delta 17) predominates in skeleta l muscle and gut and is also expressed in bladder, fat, heart, lung, liver, and kidney. Polymerase chain reaction and restriction digest analysis of s ur2 cDNA demonstrate the existence of at least five sur2 splice variants as follows: SUR2(39), SUR2(40), SUR2(Delta 17/39), SUR2(Delta 17/40), and SUR 2(Delta 14/39). Electrophysiological recordings of excised, inside-out patc hes from COS cells cotransfected with Kir6.2 and the sur2 variants demonstr ated that exon 17 splicing alters KATP sensitivity to ATP block, by a;fold hom;approximate to 40 to approximate to 90 mu M for exon 17 and Delta 17, r espectively. Single channel kinetic analysis of SUR2(39) and SUR2(Delta 17/ 39) demonstrated that both exhibited characteristic K-ATP kinetics but that SUR2(Delta 17/39) exhibited longer mean burst durations and shorter mean i nterburst dwell times. In sum, alternative splicing of sur2 enhances the ob served diversity of K-ATP and may contribute to tissue-specific modulation of ATP sensitivity.