Expression and function of colonic epithelial KvLQT1 K+ channels.
1. KvLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential. Defects in ion channels have been demonstrated in cardiac arrhythmia. This channel is inhibited potently by the chromanol 293B. The same compound has been shown to block cAMP-dependent electrolyte secretion in rat and human colon. Therefore, it was suggested that a K+ channel similar to KvLQT1 is expressed in the colonic epithelium. 2. In the present paper, expression of KvLQT1 and its function in colonic epithelial cells is described. Reverse transcription-polymerase chain reaction analysis of rat colonic mucosa demonstrated expression of KvLQT1 in both crypt cells and surface epithelium. When expressed in Xenopus oocytes, KvLQT1 induced a typical delayed activated K+ current. 3. As demonstrated, the channel activity could be further activated by increases in intracellular cAMP. These and other data support the concept that KvLQT1 is forming a component of the basolateral cAMP-activated K+ conductance in the colonic epithelium.
Kunzelmann
K
K
Department of Physiology and Pharmacology, University of Queensland, St Lucia, Australia. kunzelmann@plpk.uq.edu.au
Bleich
M
M
Warth
R
R
Levy-Holzman
R
R
Garty
H
H
Schreiber
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008954:Models, Biological; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014981:Xenopus
D002839:Chromans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496911:Kcnq1 protein, rat; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D019789:Tetraethylammonium; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine