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- Title
The role of KCNQ1/KCNE1 K<sup>+</sup> channels in intestine and pancreas: lessons from the KCNE1 knockout mouse.
- Authors
Warth, R.; Alzamora, M. Garcia; Kim, J. K.; Zdebik, A.; Nitschke, R.; Bleich, M.; Gerlach, U.; Barhanin, J.; Kim, S. J.
- Abstract
KCNE1 (IsK, minK) co-assembles with KCNQ1 (KvLQT1) to form voltage-dependent K+ channels. Both KCNQ1 and KCNE1 are expressed in epithelial cells of gut and exocrine pancreas. We examined the role of KCNQ1/KCNE1 in Cl– secretion in small and large intestine and exocrine pancreas using the KCNE1 knockout mouse. Immunofluorescence revealed a similar basolateral localization of KCNQ1 in jejunum and colon of KCNE1 wild-type and knockout mice. Electrogenic Cl– secretion in the colon was not affected by gene disruption of KCNE1; in jejunum forskolin-induced short-circuit current was some 40% smaller but without being significantly different. Inhibition of KCNQ1 channels by 293B (IC50 1 µmol l–1) and by IKS224 (IC50 14 nmol l–1) strongly diminished intestinal Cl– secretion. In exocrine pancreas of wild-type mice, KCNQ1 was predominantly located at the basolateral membrane. In KCNE1 knockout mice, however, the basolateral staining was less pronounced and the distribution of secretory granules was irregular. A slowly activating and 293B-sensitive K+ current was activated via cholinergic stimulation in pancreatic acinar cells of wild-type mice. In KCNE1 knockout mice this K+ current was strongly reduced. In conclusion intestinal Cl– secretion is independent from KCNE1 but requires KCNQ1. In mouse pancreatic acini KCNQ1 probably co-assembled with KCNE1 leads to a voltage-dependent K+ current that might be of importance for electrolyte and enzyme secretion.
- Subjects
ION channels; EPITHELIAL cells; JEJUNUM; PANCREATIC acinar cells; LABORATORY mice; ENZYMES
- Publication
Pflügers Archiv: European Journal of Physiology, 2002, Vol 443, Issue 5/6, p822
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-001-0751-3