PMID- 10224138
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 19
DP  - 1999 May 7
TI  - Alternative splicing of sur2 Exon 17 regulates nucleotide sensitivity of the
      ATP-sensitive potassium channel.
PG  - 13656-65
AB  - ATP-sensitive potassium channels (KATP) 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 KATP 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(Delta17) 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(Delta17/39), SUR2(Delta17/40), and SUR2(Delta14/39). 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 2-fold from approximately 40 to approximately 90
      microM for exon 17 and Delta17, respectively. Single channel kinetic analysis of 
      SUR2(39) and SUR2(Delta17/39) demonstrated that both exhibited characteristic
      KATP kinetics but that SUR2(Delta17/39) exhibited longer mean burst durations and
      shorter mean interburst dwell times. In sum, alternative splicing of sur2
      enhances the observed diversity of KATP and may contribute to tissue-specific
      modulation of ATP sensitivity.
FAU - Chutkow, W A
AU  - Chutkow WA
AD  - Departments of Medicine and Pharmacological and Physiological Sciences, the
      University of Chicago, Chicago, Illinois 60637, USA.
FAU - Makielski, J C
AU  - Makielski JC
FAU - Nelson, D J
AU  - Nelson DJ
FAU - Burant, C F
AU  - Burant CF
FAU - Fan, Z
AU  - Fan Z
LA  - eng
GR  - DK-K08-02170/DK/NIDDK NIH HHS/United States
GR  - R01-HL57414/HL/NHLBI NIH HHS/United States
GR  - R29 HL58133-01/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (DNA Primers)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Receptors, Drug)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfonylurea Receptors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.- (Mixed Function Oxygenases)
SB  - IM
MH  - *ATP-Binding Cassette Transporters
MH  - Adenosine Triphosphate/*pharmacology
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - *Exons
MH  - Mice
MH  - Mixed Function Oxygenases/chemistry/*genetics
MH  - Molecular Sequence Data
MH  - Potassium Channels/*drug effects/physiology
MH  - Potassium Channels, Inwardly Rectifying
MH  - Receptors, Drug
MH  - Recombinant Proteins/drug effects
MH  - Sulfonylurea Receptors
EDAT- 1999/05/01 00:00
MHDA- 1999/05/01 00:01
CRDT- 1999/05/01 00:00
PHST- 1999/05/01 00:00 [pubmed]
PHST- 1999/05/01 00:01 [medline]
PHST- 1999/05/01 00:00 [entrez]
AID - 10.1074/jbc.274.19.13656 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 7;274(19):13656-65. doi: 10.1074/jbc.274.19.13656.