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

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...

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Published in:Journal of pharmacy and pharmacology 2003-04, Vol.55 (4), p.527-531
Main Author: Burleigh, David E.
Format: Article
Language:English
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Summary: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.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357021008