Cloning and Function of the Rat Colonic Epithelial K+ Channel KVLQT1 |
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Authors: | K Kunzelmann M Hübner R Schreiber R Levy-Holzman H Garty M Bleich R Warth M Slavik T von Hahn R Greger |
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Institution: | Department of Physiology & Pharmacology, University of Queensland St Lucia, Brisbane, Australia. |
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Abstract: | 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.
Received: 17 July 2000/Revised: 25 October 2000 |
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Keywords: | : rKVLQT1 — rKCNQ1 — Rat colon — K+ channel — Epithelium — Electrolyte secretion — Ion transport — Xenopus oocytes — Expression — Cloning — Ussing chamber |
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