External anions modify the anion/proton transport stoichiometry. (A) Pulse protocol and representative ClC-4 whole cell current traces in standard Cl⁻-based intracellular and extracellular solutions. (B) Time courses of intracellular pH changes at the same cell at various test potentials. Red lines show linear fits to obtain ΔpH/Δt. (C) Current–voltage dependences measured for various external anions with Cl⁻ intracellular solution. Cells were sequentially perfused with different extracellular anions, and current amplitudes were normalized to currents determined in Cl⁻-based external solution (n = 4–6). (D) Rates of intracellular pH change in the same cells as in C normalized to values obtained in Cl⁻-based external solution. (E) Relative current to proton flux ratio for Cl⁻, Br⁻, I⁻, NO₃⁻, and SCN⁻ at +90 mV. (F) Absolute anion to proton transport stoichiometry for Cl⁻, NO₃⁻, and SCN⁻ determined at +90 mV (n = 4–7).