Expression of the chloride channel ClC-2 in the murine small intestine epithelium |
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Authors: | Gyömörey K Yeger H Ackerley C Garami E Bear C E |
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Affiliation: | Programme in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8. |
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Abstract: | The chloride channel ClC-2 has been implicated inneonatal airway chloride secretion. To assess its role in secretion by the small intestine, we assessed its subcellular expression in ilealsegments obtained from mice and studied the chloride transport properties of this tissue. Chloride secretion across the mucosa ofmurine ileal segments was assessed in Ussing chambers as negative short-circuit current (Isc). If ClC-2contributed to chloride secretion, we predicted on the basis ofprevious studies that negative Isc would bestimulated by dilution of the mucosal bath and that this response woulddepend on chloride ion and would be blocked by the chloride channelblocker 5-nitro-2-(3-phenylpropylamino) benzoic acid but not by DIDS.In fact, mucosal hypotonicity did stimulate a chloride-dependent changein Isc that exhibited pharmacological propertiesconsistent with those of ClC-2. This secretory response is unlikely tobe mediated by the cystic fibrosis transmembrane conductance regulator(CFTR) channel because it was also observed in CFTR knockout animals.Assessment of the native expression pattern of ClC-2 protein in themurine intestinal epithelium by confocal and electron microscopy showedthat ClC-2 exhibits a novel distribution, a distribution patternsomewhat unexpected for a channel involved in chloride secretion.Immunolabeled ClC-2 was detected predominantly at the tight junctioncomplex between adjacent intestinal epithelial cells. |
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