The role of KCNQ1/KCNE1 K⁺ channels in intestine and pancreas: lessons from the KCNE1 knockout mouse

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.

Authors and Affiliations

1. IPMC, CNRS, 660 route des Lucioles, 06560 Sophia-Antipolis, France, , , , ,

   R. Warth &  J. Barhanin

2. Physiologisches Institut, Hermann-Herder-Str. 7, 79104 Freiburg, Germany, , , , ,

   M. Garcia Alzamora

3. Department of Physiology, SKKU Medical School, Suwon 440–746, Korea, , , , ,

   J. Kim &  S. Kim

4. ZMNH, Martinistr. 85, 20246 Hamburg, Germany, , , , ,

   A. Zdebik

5. Entwicklungsbiologie, Hauptstr. 1, 79104 Freiburg, Germany, , , , ,

   R. Nitschke

6. Aventis Pharma, 65926 Frankfurt, Germany, , , , ,

   M. Bleich &  U. Gerlach

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