Involvement of inwardly rectifying K+ channels in secretory responses of human ileal mucosa.
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 microM) or a combination of charybdotoxin (0.3 microM) plus apamin (0.3 microM). 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.
Burleigh
David E
DE
Department of Adult and Paediatric Gastroenterology, St Bartholomew's and The Royal London School of Medicine and Dentistry, London E1 2AD, UK. d.e.burleigh@qmul.ac.uk
D015761:4-Aminopyridine / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide
D001427:Bacterial Toxins; D017609:Barium Compounds; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C024986:barium chloride; D018999:Charybdotoxin; D001030:Apamin; D014660:Vasoactive Intestinal Peptide; D015761:4-Aminopyridine; D005905:Glyburide