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

R. Warth, M. Garcia Alzamora, J. Kim, A. Zdebik, R. Nitschke, M. Bleich, U. Gerlach, J. Barhanin, S. Kim

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

KCNE1 (IsK, minK) co-assembles with KCNQI (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.

Original languageEnglish (US)
Pages (from-to)822-828
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume443
Issue number5-6
DOIs
StatePublished - Mar 27 2002
Externally publishedYes

Keywords

  • Diarrhoea
  • IsK
  • KCNE3
  • KvLQT1
  • Mink

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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