Abstract

The roles of spontaneous and electrically stimulated neural activity on mucosal ion transport were examined in the distal jejunum of the pig, an omnivorous species whose digestive function bears similarities to that of humans. Serosal administration of the neuronal conduction blocker tetrodotoxin (TTX; 0.1 mumol/l), the presynaptic Ca channel blocker omega-conotoxin GVIA (0.1 mumol/l) and the ganglionic-blocking agent hexamethonium (0.1 mmol/l) decreased basal short-circuit current (Isc) across sheets of jejunal mucosa-submusa in vitro. The TTX-induced change in Isc was attributable to an increase in net Cl absorption. Electrical transmural stimulation (ETS; 300 pulses at 0.5, 3 or 10 Hz, 0.5-msec pulse width, 2.8 mA cm-2) of the mucosa-submucosa produced a frequency-dependent increase in Isc and an increase in net anion secretion. TTX, conotoxin and hexamethonium produced concentration-dependent decreases of the ETS-evoked increase in Isc, indicating that ETS depolarizes enteric neurons and suggesting that cholinergic neurons synapsing with submucosal neurons play a significant role in mediating ETS-evoked ion transport. The ETS-induced Isc appears to be mediated by neurons containing acetylcholine but not substance P or vasoactive intestinal polypeptide. These results suggest that submucosal noncholinergic neurons tonically limit Cl but not Na absorption. Electrical depolarization of submucosal neurons evokes anion secretion which appears to be mediated by cholinergic neurons as well as neurons of unknown chemical identity.