External Cl⁻ promotes coupled anion–proton exchange. (A) Representative intracellular pH time course at +90 mV in a ClC-4 expressing cell perfused with extracellular solutions containing 30 mM SCN⁻ and variable concentrations of Cl⁻. Solid lines represent linear fits. (B) Normalized current–voltage relationships from the same cell at extracellular solutions containing 30 mM SCN⁻ and variable concentrations of Cl⁻. (C) Variation of normalized current amplitudes and normalized proton fluxes by increasing concentrations of Cl⁻ at +90 mV (n = 4–5). Lines represent fits with standard one-site binding function (Michaelis-Menten functions). (D) Ratios of unitary transport rates of H⁺-coupled and uncoupled ClC-4 currents for different [Cl⁻] with constant [SCN⁻] at +90 mV (n = 3).