Sequential interaction of chloride and proton ions with the fast gate steer the voltage‐dependent gating in ClC‐2 chloride channels

Plasma membrane ClC‐2 chloride channels are widely distributed in our body and are important for vision and fertility. ClC‐2 channels are gated by changes in transmembrane voltage despite of lacking a voltage sensor device. It has been hypothesized that the interaction of an external proton with the gating machinery is responsible for voltage‐dependent gating. Here we used electrophysiological recordings and quantitative analysis under different external proton and internal chloride concentrations and found that the voltage dependence of gating is due to interaction between the passing chloride ion and the permeation pathway, with the external proton stabilizing the open state of the channel.

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