Different functional roles for K+ channel subtypes in regulating small intestinal glucose and ion transport

Abstract

Background: Although K+ channels are important in mediating the driving force for colonic ion transport, their role in the small intestinal transport is poorly understood. Methods: Small intestinal short circuit currents (Isc) and HCO3− secretion were measured in mice, and intracellular pH (pHi) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, Western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption. Results: KV7.1 is not involved in duodenal ion transport, while KCa3.1 selectively regulates duodenal Isc and HCO3− secretion in a Ca2+-mediated but not cAMP-mediated manner. Blockade of KCa3.1 increased the rate of HCO3− fluxes via CFTR channels in SCBN cells. Jejunal Isc was significantly stimulated by glucose, but markedly inhibited by 4-AP and TEA. Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice. Conclusions: This study not only examines the contribution of various K+ channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K+ channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus.