Diphenylamine-2-carboxylate, a blocker of the Cl(-)-conductive pathway in Cl(-)-transporting epithelia

Abstract

The present study examines the effects of diphenylamine-2-carboxylate (DPC) in Cl(-)-transporting epithelia. This substance blocks reversibly the Cl(-)-conductance present under normal circumstances in the basolateral membrane of the thick ascending limb of the loop of Henle (TAL) and in the apical membrane of shark rectal gland tubules (RGT). This leads to a reduction in active NaCl reabsorption (TAL) and NaCl secretion (RGT) respectively, as measured by the equivalent short circuit current. The cells hyperpolarize as the membrane voltage drifts from the control value (some compromise between the chemical potential of Cl- and K+) towards the chemical potential of K+. The resistance of the basolateral (TAL) or apical membrane (RGT) increases and this leads to a moderate increase in transepithelial resistance. In addition, the Cl(-)-concentration step induced membrane voltage changes, which can be produced under control conditions, disappear in the presence of the blocker. Finally, experiments in excised membrane patches indicate that this substance inhibits the single current events of individual Cl(-)-channels.