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

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.