Temperature-sensitive gating of voltage-gated proton channels.

The voltage-gated proton channel (Hv) mediates robust proton transport down the proton electrochemical gradient. Hv is mainly expressed in immune cells, including neutrophils and macrophages, the physiological functions of which are temperature sensitive. In those cells, Hv plays key roles in the regulation of reactive oxygen species production and pH homeostasis. Proton transport through Hv is regulated by both the membrane potential and the pH difference across the cell membrane. Earlier studies showed that the properties of Hv, including proton conductance and gating, are highly temperature dependent. Hv consists of a voltage sensor domain involved in both voltage sensing and proton permeation and a C-terminal coiled coil region. Although the channel's activities are innate to the protomers, normally two protomers assemble as a dimer via interaction between C-terminal coiled coils. We recently discovered that the coiled-coil region of Hv dissociates at around room temperature, and that subtle changes in the coiled-coil region affect temperature-sensitive gating. In this chapter, we describe the physiological functions and molecular mechanisms of Hv, focusing mainly on the structure and thermosensitive properties of Hv.