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Abstract:
The voltage-gated proton channel Hv1 is expressed in a variety of cells, including macrophages,
sperm, and lung epithelial cells. Hv1 is gated by both the membrane potential and the diference
between the intra- and extracellular pH (ΔpH). The coupling of voltage- and ∆pH-sensing is such
that Hv1 opens only when the electrochemical proton gradient is outwardly directed. However, the
molecular mechanism of this coupling is not known. Here, we investigate the coupling between
voltage- and ΔpH-sensing of Ciona intestinalis proton channel (ciHv1) using patch-clamp fuorometry
(PCF) and proton uncaging. We show that changes in ΔpH can induce conformational changes of the
S4 voltage sensor. Our results are consistent with the idea that S4 can detect both voltage and ΔpH.