## Abstract

The mechanism of Cl<latex>$^-$</latex> secretion in the isolated, resting (i.e. cimetidine-treated) gastric mucosa of Necturus has been investigated with radioisotopic and electrophysiological techniques. Measurement of transepithelial <latex>$^{36}$</latex>Cl<latex>$^-$</latex> fluxes (mucosal to serosal (M <latex>$\rightarrow $</latex>S), J<latex>$^{Cl-}_{ms}$</latex>; S <latex>$\rightarrow$</latex> M, J<latex>$^{Cl-}_{sm}$</latex>) during control conditions show that at open circuit, when the transepithelial potential difference <latex>$\psi_{ms}$</latex> = 20 mV (S ground), J<latex>$^{Cl-}_{ms}$</latex> = J<latex>$^{Cl-}_{sm}$</latex>, i.e. J<latex>$^{Cl-}_{net}$</latex> = 0, but during short-circuit current conditions J<latex>$^{Cl-}_{net}$</latex> = I<latex>$_{se}$</latex> = 2 <latex>$\mu$</latex> equiv cm<latex>$^{-2}$</latex> h. Experiments with low [Cl<latex>$^-$</latex>] solutions indicate that Cl<latex>$^-$</latex> exchange diffusion does not contribute significantly to either J<latex>$^{Cl-}_{ms}$</latex> or J<latex>$^{Cl-}_{sm}$</latex>. Double-barrelled, Cl<latex>$^-$</latex>-selective microelectrodes showed that in open circuit, the cellular (C) chemical potential for Cl<latex>$^-$</latex>, <latex>$\psi^{Cl-}_c$</latex> = 31 mV (apparent [Cl<latex>$^-$</latex>] = 29 mM), the electrical potential across the M membrane, <latex>$\psi_m$</latex> = -34 mV (mucosa ground) while that across the S membrane, <latex>$\psi_s$</latex> = -52 mV (serosa ground). During short-circuit current conditions, <latex>$\psi_m$</latex> = <latex>$\psi_s$</latex> = -49 mV and [Cl<latex>$^-$</latex>]<latex>$_c$</latex> = 30 mM. The permeability of the M membrane to Cl<latex>$^-$</latex> (P<latex>$^{Cl-}_m$</latex>) was calculated both from the tracer experiments and the electrode measurements by using the constantfield equation. Short-term (45 s) uptake of <latex>$^{36}$</latex>Cl<latex>$^-$</latex> at [Cl<latex>$^-$</latex>]<latex>$_m$</latex> = 96 mM during short circuit conditions gave P<latex>$^{Cl-}_m$</latex> = 2.6 10<latex>$^{-5}$</latex> cm s<latex>$^{-1}$</latex>. Measurement of [Cl<latex>$^-$</latex>]<latex>$_c$</latex> by means of the electrodes when [Cl<latex>$^-$</latex>]<latex>$_m$</latex> was changed from 96 to 2 mM or from 2 to 96 mM gave P<latex>$^{Cl-}_m$</latex> = 2.9-5.7 10<latex>$^{-5}$</latex> cm s<latex>$^{-1}$</latex>. Our results indicate that during open circuit conditions Cl<latex>$^-$</latex> is accumulated across the S membrane into gastric cells in an energy-requiring step, but since J<latex>$^{Cl-}_net$</latex> = 0, Cl<latex>$^-$</latex> must leak back into the S solution at a rate equal to the entry rate. When the tissue is short-circuited, Cl<latex>$^-$</latex> secretion occurs (J<latex>$^{Cl-}_{net}$</latex> = I<latex>$_{se}$</latex>) owing to the same energy-requiring accumulation of Cl<latex>$^-$</latex> by the cells and a passive (apparently electrodiffusive) movement across the mucosal membrane.