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 subunit,, 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 skeletal muscle and gut and is also expressed in bladder, fat, heart, lung, liver, and kidney. Polymerase chain reaction and restriction digest analysis of sur2 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 SUR2(Delta 14/39). Electrophysiological recordings of excised, inside-out patches from COS cells cotransfected with Kir6.2 and the sur2 variants demonstrated 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, respectively. 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 interburst dwell times. In sum, alternative splicing of sur2 enhances the observed diversity of K-ATP and may contribute to tissue-specific modulation of ATP sensitivity.