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

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 (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.

Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice

“…1A-F, in pancreas, KCNQ1 antibodies not only strongly labeled acinar cells in a similar pattern as described before 20 but also yielded good staining in insulin-positive cells, indicating the expression of KCNQ1 protein in pancreatic b-cells. In intestine (Fig.…”

“…19,20,26,27 By several GWA studies, KCNQ1 has been identified as a transethnic susceptibility gene for T2D. 6 Genetic variation in KCNQ1 appears to be associated with impaired insulin secretion.…”

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

“…In the pancreas, KCNQ1 is co-expressed with products of other regulators, such as KCNE1, which may alter both its biophysical characteristics and its role. 25 As such, it is plausible that polymorphisms within the KCNQ1 gene alter the properties and role of the I KS K + channel, causing decreased pancreatic b cell function and insulin production, KCNQ1 genetic variants predict future T2DM Se Eun Park et al eventually leading to hyperglycemia. Although the function of KCNQ1 in the pancreatic b cell is not fully understood, several discrepancies have been noted about the relationship between the KCNQ1 variants and pancreatic b cell function.…”

Protein distribution of Kcnq1, Kcnh2, and Kcne3 potassium channel subunits during mouse embryonic development

“…These observations suggest that specific potassium conductance-mediated contraction is unique for the intestinal tract at least at early stages of development. In the same line, Kcnh2 seems to be the prominent pore-forming subunit expressed in the developing gut, whereas in the adult intestinal epithelia Kcnq1 is widely documented (Delomombe et al, 2001;Warth et al, 2002). This discrepancy might be due to progressive shift in the potassium modulation requirements of the developing intestinal epithelial as maturation processes.…”