Regulation des Kaliumtransportes durch das Zellvolumen

Abstract

The intestinal potassium transport is under the control of many second messenger systems (for example cAMP and Ca²⁺). Another pathway that influences Na⁺- and Cl^--transport is the cell volume. Volume-activated K⁺-channels are present in the basolateral membrane of colonic crypts. Therefore the aim of this work was to investigate if there is a volume influence at the transepithelial K⁺ transport.

The effect of cell swelling and cell shrinkage on K⁺ transport across the rat colonic epithelium was studied by measuring unidirectional fluxes, uptake and efflux of ⁸⁶Rb⁺, a marker for K⁺.

Exposure to a hypotonic medium stimulated the secretory, serosa-to-mucosa flux of K⁺, whereas exposure to a hypertonic medium inhibited the absorptive, mucosa-to-serosa flux of K⁺ in the distal, but not in the proximal colon. Neither manoeuvre had any effect on the uptake of K⁺ across the apical or the basolateral membrane.

Cell swelling stimulated apical and basolateral K⁺ efflux in both colonic segments, whereas cell shrinkage reduced it. The stimulation of the swelling-induced K⁺ efflux in the distal colon is Ba²⁺ sensitive at the apical side and quinine sensitive at the basolateral side. Incubation of the tissue in Ca²⁺-free buffer and La³⁺, which blocks Ca²⁺-influx into the epithelium side, strongly reduced the basal K⁺ efflux across the basolateral membrane. The same was observed with brefeldin A, a blocker of the transport of newly synthesized proteins out of the endoplasmatic reticulum. Swelling-induced K⁺ efflux, however, was not reduced. Hypotonically-stimulated apical K⁺ efflux was enhanced by drugs disturbing the cytoskeleton such as colchicine, an inhibitor of the polymerisation of microtubules, and by brefeldin A.

These results demonstrate that the cell volume is involved in the regulation of transepithelial K⁺ transport across the rat colonic epithelium and suggest a role of Ca²⁺ and the cytoskeleton in the control of a part of the volume-sensitive K⁺ channels.