Active absorption of NH₄⁺ by rat medullary thick ascending limb: Inhibition by potassium

These experiments were designed to determine the relative contributions of active NH₄⁺ transport and voltage-driven NH₄⁺ diffusion to direct NH₄⁺ absorption by the medullary thick ascending limb of the rat. Medullary thick ascending limbs were perfused in vitro with solutions containing 25 mM HCO₃ and 4 mM total ammonia. Under steady-state conditions, the lumen-positive transepithelial voltage (V(T)) was not sufficient to account for the observed decrease in lumen NH₄⁺ concentration, consistent with active absorption of NH₄⁺. Flux calculations based on V(T) and measured NH₄⁺ permeability (6 x 10^-5 cm/s) indicate that the majority (at least 65%) of total ammonia absorption is due to active transport of NH₄⁺. The remainder of NH₄⁺ absorption can be accounted for by voltage-driven diffusion. Increasing the potassium concentration from 4 to 24 mM in perfusate and bath markedly inhibited total ammonia absorption but did not affect V(T), NH₄⁺ permeability, or HCO₃ absorption. These results are consistent with inhibition of the active component of NH₄⁺ absorption by potassium. The active NH₄⁺ absorption is likely mediated by cotransport of Na⁺, NH₄⁺, and Cl^- across the apical cell membrane. Inhibition of active NH₄⁺ absorption by an increase in potassium concentration may be due, in part, to competition between NH₄⁺ and K⁺ for a common binding site on the Na⁺-K⁺-2Cl^- cotransport system.