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

• Published in: Pflügers Archiv 2002-03, Vol.443 (5-6), p.822-828
• Main Authors: Warth, R, Garcia Alzamora, M, Kim, J K, Zdebik, A, Nitschke, R, Bleich, M, Gerlach, U, Barhanin, J, Kim, S J
• Format: Article
• Language: English
• Subjects: Animals; Chlorides - metabolism; Colon - metabolism; Colon - secretion; Intestinal Mucosa - chemistry; Intestinal Mucosa - metabolism; Intestinal Mucosa - secretion; Jejunum - metabolism; Jejunum - secretion; KCNQ Potassium Channels; KCNQ1 Potassium Channel; Membrane Potentials - physiology; Mice; Mice, Knockout; Pancreas; Pancreas - chemistry; Pancreas - metabolism; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels - analysis; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Voltage-Gated; Rodents
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-001-0751-3

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 (IC(50) 1 micromol l(-1)) and by IKS224 (IC(50) 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.