Cholinergic regulation of salt absorption by turtle colon: Dual control of sodium and chloride transport.

It has long been recognized that stimulating cholinergic nerves or exposure to exogenous cholinergic agonists decreases the absorption of salt and water across intestinal epithelium, but little is known about the underlying cellular mechanisms. The turtle colon provides a convenient model to study the cellular mechanisms that underlie the cholinergic regulation of salt absorption since it appears to consist of a single population of Na-absorbing cells, in which the active (electrogenic) absorption of Na produces a serosa-positive electrical potential difference that drives the passive absorption of Cl via cellular and paracellular shunt pathways. Isolated portions of turtle colons were mounted as flat sheets in conventional Ussing chambers and voltage clamped to zero mV. The addition of exogenous muscarinic cholinergic agonists resulted in two distinct transport effects. Active Na absorption was reduced and the transmural conductance to Cl was markedly attenuated. These results provide the first evidence for dual mechanisms for the regulation of Na and Cl transport. The role of the basolateral membrane of the epithelial cell in these regulatory responses was studied using tissues treated with the pore-forming antibiotic amphotericin B to eliminate the apical membrane as a barrier to cation flow. Muscarinic cholinergic agonists produced a sustained inhibition of the K and Cl conductances of the basolateral membrane. The former effect is sufficient to reduce active Na absorption and the latter would be expected to reduce transmural Cl flow. The addition of the calcium ionophores A23187 and ionomycin mimicked the cholinergic response, suggesting that it was mediated by a change in intracellular Ca$\\sp{+2}$. Experimental manuevers that were presumed to depolarize neurons evoked changes in basolateral K conductance that were identical to those produced by exogenous cholinergic agonists. These results are consistent with the notion that the submucosa and /or mucosa contains a population of cholinergic neurons that exert a regulatory effect on salt absorption.Ph.D.Animal PhysiologyBiophysicsBiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/161876/1/8813013.pd