Voltage-dependent gating of ClC-4. (A) Schematic representation of voltage clamp protocols as well as predicted ClC-4 whole cell current and the proton currents for gated and not-gated exchanger function. Voltage steps were repetitively applied with TP and TI denoting pulse and interpulse duration. QP gives transported charge during a single depolarizing voltage step. (B) Representative intracellular pH recordings from ClC-4–expressing cells stimulated with different voltage protocols. The top panel compares intracellular alkalinization elicited by two protocols with identical total pulse (
) and total interpulse (
) durations,
(Tshort) or
(Tlong), respectively. The bottom panel compares intracellular alkalinization elicited by protocols that differ in total pulse (
) and total interpulse (
) durations but exhibit equal total transported charge (
). For “Q short,” TP and TI equal 1.5 ms, whereas “Q long” denotes a pulse protocol with
and
In the protocol “Q2 = 1.5 QT,”
and
resulting in total transported charge,
which is 1.5 times larger compared with pulse protocols “Q short” and “Q long.” (C) Statistical analysis of pH responses in several cells (n = 4–6).