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

William A. Chutkow, Jonathan C. Makielski, Deborah J. Nelson, Charles F. Burant, Zheng Fan

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Abstract

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(Δ17) 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(Δ17/39), SUR2(Δ17/40), and SUR2(Δ14/39). Electrophysiological recordings of excised, inside-out patches from COS cells cotransfected with Kir6.2 and the sur2 variants demonstrated that exon 17 splicing alters K(ATP) sensitivity to ATP block by 2-fold from ≃40 to ≃90 μM for exon 17 and Δ17, respectively. Single channel kinetic analysis of SUR2(39) and SUR2(Δ17/39) demonstrated that both exhibited characteristic K(ATP) kinetics but that SUR2(Δ17/39) 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.

Original languageEnglish (US)
Pages (from-to)13656-13665
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number19
DOIs
StatePublished - May 7 1999

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KATP Channels
Alternative Splicing
Exons
Nucleotides
Adenosine Triphosphate
Muscle
Tissue
Kinetics
COS Cells
Polymerase chain reaction
Ribonucleases
Liver
Skeletal Muscle
Urinary Bladder
Complementary DNA
Fats
Modulation
Kidney
Muscles
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Alternative splicing of sur2 exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. / Chutkow, William A.; Makielski, Jonathan C.; Nelson, Deborah J.; Burant, Charles F.; Fan, Zheng.

In: Journal of Biological Chemistry, Vol. 274, No. 19, 07.05.1999, p. 13656-13665.

Research output: Contribution to journalArticle

Chutkow, William A. ; Makielski, Jonathan C. ; Nelson, Deborah J. ; Burant, Charles F. ; Fan, Zheng. / Alternative splicing of sur2 exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 19. pp. 13656-13665.
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