Article: article from journal or magazin.
Cloning and function of the rat colonic epithelial K+ channel KVLQT1.
Journal of Membrane Biology
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
KVLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential that is defective in cardiac arrhythmia. The channel is inhibited by the chromanol 293B, a compound that blocks cAMP-dependent electrolyte secretion in rat and human colon, therefore suggesting expression of a similar type of K+ channel in the colonic epithelium. We now report cloning and expression of KVLQT1 from rat colon. Overlapping clones identified by cDNA-library screening were combined to a full length cDNA that shares high sequence homology to KVLQT1 cloned from other species. RT-PCR analysis of rat colonic musoca demonstrated expression of KVLQT1 in crypt cells and surface epithelium. Expression of rKVLQT1 in Xenopus oocytes induced a typical delayed activated K+ current, that was further activated by increase of intracellular cAMP but not Ca2+ and that was blocked by the chromanol 293B. The same compound blocked a basolateral cAMP-activated K+ conductance in the colonic mucosal epithelium and inhibited whole cell K+ currents in patch-clamp experiments on isolated colonic crypts. We conclude that KVLQT1 is forming an important component of the basolateral cAMP-activated K+ conductance in the colonic epithelium and plays a crucial role in diseases like secretory diarrhea and cystic fibrosis.
1-Methyl-3-isobutylxanthine/pharmacology, Amino Acid Sequence, Animals, Barium/pharmacology, Carbachol/pharmacology, Cardiotonic Agents/pharmacology, Cloning, Molecular, Colon/metabolism, Cyclic AMP/metabolism, Dinoprostone/pharmacology, Forskolin/pharmacology, Humans, Intestinal Mucosa/cytology, Intestinal Mucosa/drug effects, KCNQ Potassium Channels, KCNQ1 Potassium Channel, Male, Molecular Sequence Data, Oocytes/physiology, Patch-Clamp Techniques, Phosphodiesterase Inhibitors/pharmacology, Potassium Channels/chemistry, Potassium Channels/genetics, Potassium Channels, Voltage-Gated, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Sequence Alignment, Tetraethylammonium/pharmacology, Xenopus laevis
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