Involvement of inwardly rectifying K+ channels in secretory responses of human ileal mucosa

Abstract

Abstract In acute secretory diarrhoea the primary event driving fluid secretion is a transcellular, electrogenic, serosal to mucosal transport of chloride ions. Such transport requires the maintenance of an electrically negative cell membrane voltage, which is achieved through a basolateral outward leakage of potassium ions. The aim of this study was to investigate the nature of K+ channel involvement in facilitating secretory processes in the human ileum. Muscle-stripped mucosal preparations of human ileal mucosa were set up in Ussing chambers for recording short-circuit current and transmucosal conductance. Escherichia coli heat-stable toxin and vasoactive intestinal peptide (VIP) produced concentration-dependent increases in short-circuit current. Responses to the heat- stable toxin were unaffected by basolateral application of 4-aminopyridine (5 mm), glibenclamide (10 μm) or a combination of charybdotoxin (0.3 μ m) plus apamin (0.3 μm). However, basolateral barium (0.2–5 mm) caused a concentration-dependent inhibition. Responses to VIP were similarly affected by barium (0.05–1 mm). These results suggested that electrogenic chloride transport by human ileal mucosa required the presence of basolateral K+ channels. The use of selective K+-channel inhibitors and low concentrations of barium suggested that the channels involved might be of the inwardly rectifying type.