Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease.
We have cloned a novel member of the CLC chloride channel family from rat brain, rCLC-5. The cDNA predicts a 83-kDa protein belonging to the branch including CLC-3 and CLC-4, with which it shares approximately 80% identity. Expression of rCLC-5 in Xenopus oocytes elicits novel anion currents. They are strongly outwardly rectifying and have a conductivity sequence of NO3- > Cl- > Br- > I- >> glutamate-. Although CLC-5 has consensus sites for phosphorylation by protein kinase A, raising the intracellular cAMP concentration had no effect on these currents. Currents were also unchanged when rCLC-5 was coexpressed with rCLC-3 and rCLC-4, either singly or in combination. rCLC-5 is expressed predominantly in kidney and also in brain, lung, and liver. Along the nephron, rCLC-5 message is detectable in all tubule segments investigated, but expression in the glomerulus and the S2 segment of the proximal tubule is low.
Center for Molecular Neurobiology, Hamburg University, Federal Republic of Germany.
K
K
Steinmeyer
B
B
Schwappach
M
M
Bens
A
A
Vandewalle
T J
TJ
Jentsch
D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary; D007674:Kidney Diseases / Q000235:genetics*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
C097503:CLC-5 chloride channel; D018118:Chloride Channels; D017931:DNA Primers; D018076:DNA, Complementary; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases