Mechanisms of carbachol-induced alterations in K + transport across the rat colon

Abstract

The effect of carbachol, an agonist of the Ca 2+ pathway, on K + transport in rat proximal and distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb +, a marker for K +, in mucosa–submucosa preparations. Unidirectional ion flux measurements revealed that carbachol stimulated K + secretion in the proximal colon by a marked increase in the serosa-to-mucosa flux ( J sm Rb) and a more moderate rise in the mucosa-to-serosa flux ( J ms Rb). In the distal colon carbachol had no effect on J ms Rb, but J sm Rb was reduced after a transient increase finally resulting in an inhibition of K + secretion. Carbachol caused a stimulation of mucosal Rb + uptake in the distal colon, which was diminished in the presence of inhibitors of the apical H +–K +-ATPase, vanadate and ouabain. In contrast, in the proximal colon the serosal Rb + uptake was enhanced by carbachol, an effect, which could be prevented by bumetanide, an inhibitor of the basolateral Na +–K +–2Cl −-cotransporter. Efflux experiments revealed that carbachol caused a transient increase of apical and basolateral Rb + permeability in both colonic segments. In the distal colon, stimulated K + efflux to the serosal side was reduced by quinine, efflux to the mucosal side was blocked by tetraethylammonium. In the proximal colon, carbachol-activated apical and basolateral K + efflux were inhibited by Ba 2+. In conclusion, these data suggest that in the distal colon carbachol stimulates the H +–K +-ATPase and the basolateral K + efflux through quinine-sensitive K + channels, whereas in the proximal colon carbachol induces K + secretion due to a stimulation of the basolateral Na +–K +–2Cl −-cotransporter and an increased efflux to the luminal side via Ba 2+-sensitive apical K + channels.