Serosal application of Ba(2+) induces oscillatory chloride secretion via activation of submucosal cholinergic neurones in guinea-pig distal colon.

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 (Ba(2+)), a potassium (K(+)) channel inhibitor, caused oscillatory increases in short-circuit current (I(sc)). Mean values of the size and frequency of I(sc) were 369.1 microA cm(-2) and 2.3 min(-1). The oscillatory I(sc) induced by the low concentrations of Ba(2+) was blocked by either higher concentrations of Ba(2+) (2-5 mM) or other K(+) channel inhibitors, such as tetraethylammonium (TEA) (1 mM) and quinine (20 mM). The Ba(2+)-induced oscillatory I(sc) was also inhibited by tetrodotoxin (TTX) and atropine. In a nominally Ca(2+) free solution plus serosal addition of 0.1 mM ethylene glycol-bis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), a Ca(2+) chelator, the oscillatory I(sc) slowed and diminished. Further, the Ba(2+)-induced oscillatory I(sc) was partially inhibited by apical addition of 100 microM 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 H(2) receptor antagonist, or hexamethonium, a nicotinic antagonist, to the serosal side did not affect the Ba(2+)-induced oscillatory I(sc). In conclusion, the Ba(2+)-induced oscillatory I(sc) is the transepithelial Cl(-) current which is stimulated by activation of cholinergic neurones in submucosal plexus of guinea-pig distal colon.