Activation of calcium and cAMP sensitive K+ channels in murine colonic epithelia by 1-ethyl-2-benindazolone

Cuthbert, A. W., Hickman, M., Thorn, P. and MacVinish, L. (1999) Activation of calcium and cAMP sensitive K+ channels in murine colonic epithelia by 1-ethyl-2-benindazolone. American Journal of Physiology- Cell Physiology, 277 1: C111-C120.


Author Cuthbert, A. W.
Hickman, M.
Thorn, P.
MacVinish, L.
Title Activation of calcium and cAMP sensitive K+ channels in murine colonic epithelia by 1-ethyl-2-benindazolone
Journal name American Journal of Physiology- Cell Physiology   Check publisher's open access policy
ISSN 0002-9513
Publication date 1999-07
Sub-type Article (original research)
Volume 277
Issue 1
Start page C111
End page C120
Total pages 10
Place of publication Washington, D.C
Publisher American Physiological Society
Language eng
Subject 270602 Animal Physiology - Cell
Abstract 1-Ethyl-2-benzimidazolone (EBIO) caused a sustained increase in electrogenic Cl- secretion in isolated mouse colon mucosae, an effect reduced by blocking basolateral K+ channels. The Ca2+-sensitive K+ channel blocker charybdotoxin (ChTX) and the cAMP-sensitive K+ channel blocker 293B were more effective when the other had been added first, suggesting that both types of K+ channel were activated. EBIO did not cause Cl- secretion in cystic fibrosis (CF) colonic epithelia. In apically permeabilized colonic mucosae, EBIO increased the K+ current when a concentration gradient was imposed, an effect that was completely sensitive to ChTX. No current sensitive to trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane (293B) was found in this condition. However, the presence of basolateral cAMP-sensitive K+ channels was demonstrated by the development of a 293B-sensitive K+ current after cAMP application in permeabilized mucosae. In isolated colonic crypts EBIO increased cAMP content but had no effect on intracellular Ca2+. It is concluded that EBIO stimulates Cl- secretion by activating Ca2+-sensitive and cAMP-sensitive K+ channels, thereby hyperpolarizing the apical membrane, which increases the electrical gradient for Cl- efflux through the CF transmembrane conductance regulator (CFTR). CFTR is also activated by the accumulation of cAMP as well as by direct activation.
Keyword colonic electrogenic chloride secretion
cystic fibrosis transmembrane conductance regulator
charybdotoxin
293B
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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