Molecular characterization of human SUR2-containing K(ATP) channels.
The distribution of human sulfonylurea receptor-2 (SUR2)-containing K(ATP) channels was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). mRNA for SUR2B was detected in a variety of tissues including brain, skeletal, cardiac and smooth muscle, whereas SUR2A message was restricted to cardiac and skeletal muscle. An additional splice variant of SUR2 that lacked exon 17 was also identified by RT-PCR in tissues expressing both SUR2A and SUR2B or SUR2B alone. Quantification of RNA for SUR2 exon 17+ and SUR2 exon 17- splice variants using real-time Taqman PCR indicated differential levels of expression in brain, kidney, skeletal muscle, heart and small intestine. Interestingly, the SUR2 exon 17+ variant is the major species expressed in all tissues examined in this study. Each of the SUR2 splice variants transiently expressed with the inward rectifier Kir 6.2 formed functional K(ATP) channels in HEK 293 cells as assessed either by changes in DiBAC(4)(3) fluorescence responses or glyburide-sensitive whole cell currents. Collectively, our findings demonstrate that various SUR2 splice variants have distinct expression patterns and can form functional K(ATP) channels.
Davis-Taber
R
R
Neurological and Urological Diseases Research, Dept. 47C, APgA, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Choi
W
W
Feng
J
J
Hoogenboom
L
L
McNally
T
T
Kroeger
P
P
Shieh
C C
CC
Simmer
R
R
Brioni
J D
JD
Sullivan
J P
JP
Gopalakrishnan
M
M
Scott
V E
VE
D018528:ATP-Binding Cassette Transporters; D017398:Alternative Splicing; D002460:Cell Line; D003001:Cloning, Molecular; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011955:Receptors, Drug / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution; D014162:Transfection
C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D004274:DNA, Recombinant; D006146:Guanidines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D011725:Pyridines; D012333:RNA, Messenger; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine