The enteric nervous system regulates ion and fluid secretion in the mammalian intestine at both resting and stimulated conditions. To determine the type and activation mechanism of neurones involved, mucosa-submucosa sheets isolated from guinea-pig distal colon were studied in vitro in Ussing chambers. Serosal addition of 0.5-1 mM barium (Ba2+), a potassium (K+) channel inhibitor, caused oscillatory increases in short-circuit current (/sc). Mean values of the size and frequency of /sc were 369. 1 μA cm-2 and 2.3 min-1. The oscillatory /sc induced by the low concentrations of Ba2+ was blocked by either higher concentrations of Ba2+ (2-5 mM) or other K+ channel inhibitors, such as tetraethylammonium (TEA) (1 mM) and quinine (20 mM). The Ba2+-induced oscillatory /sc was also inhibited by tetrodotoxin (TTX) and atropine. In a nominally Ca2+ free solution plus serosal addition of 0.1 mM ethylene glycol-bis (β-aminoethyl ether) N, N, N′, N′-tetraacetic acid (EGTA), a Ca2+ chelator, the oscillatory /sc slowed and diminished. Further, the Ba2+-induced oscillatory /sc was partially inhibited by apical addition of 100 μM 5′-nitro-2-(3-phenylpropylamino)benzoic-acid (NPPB), a Cl- channel inhibitor, and completely disappeared in a low Cl- solution (11 mM) on both sides. On the other hand, application of either cimetidine, a histamine H2 receptor antagonist, or hexamethonium, a nicotinic antagonist, to the serosal side did not affect the Ba2+-induced oscillatory /sc. In conclusion, the Ba2+-induced oscillatory /sc is the transepithelial Cl- current which is stimulated by activation of cholinergic neurones in submucosal plexus of guinea-pig distal colon.
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