Na⁺ and Cl⁻ conductances are controlled by cytosolic Cl⁻ concentration in the intralobular duct cells of mouse mandibular glands

Abstract

Our previously published whole-cell patch-clamp studies on the cells of the intralobular (granular) ducts of the mandibular glands of male mice revealed the presence of an amiloride-sensitive Na⁺ conductance in the plasma membrane. In this study we demonstrate the presence also of a Cl⁻ conductance and we show that the sizes of both conductances vary with the Cl⁻ concentration of the fluid bathing the cytosolic surface of the plasma membrane. As the cytosolic Cl⁻ concentration rises from 5 to 150 mmol/liter, the size of the inward Na⁺ current declines, the decline being half-maximal when the Cl⁻ concentration is approximately 50 mmol/liter. In contrast, as cytosolic Cl⁻ concentration increases, the inward Cl⁻ current remains at a constant low level until the Cl⁻ concentration exceeds 80 mmol/liter, when it begins to increase. Studies in which Cl⁻ in the pipette solution was replaced by other anions indicate that the Na⁺ current is suppressed by intracellular Br^-, Cl⁻ and NO ^-₃ but not by intracellular I^-, glutamate or gluconate. Our studies also show that the Cl⁻ conductance allows passage of Cl⁻ and Br^- equally well, I-less well, and NO ^-₃ , glutamate and gluconate poorly, if at all. The findings with NO ^-₃ are of particular interest because they show that suppression of the Na⁺ current by a high intracellular concentration of a particular anion does not depend on actual passage of that anion through the Cl⁻ conductance. In mouse granular duct cells there is, thus, a reciprocal regulation of Na⁺ and Cl⁻ conductances by the cytosolic Cl⁻ concentration. Since the cytosolic Cl⁻ concentration is closely correlated with cell volume in many epithelia, this reciprocal regulation of Na⁺ and Cl⁻ conductances may provide a mechanism by which ductal Na⁺ and Cl transport rates are adjusted so as to maintain a stable cell volume.