Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.
Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, and macrophages) during the respiratory burst. When bacteria or other microbes are engulfed by phagocytes, the enzyme NADPH oxidase assembles in the membrane and begins to produce reactive oxygen species (ROS) that help kill bacteria. NADPH oxidase is electrogenic, moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.
A group of small molecule inhibitors of the Hv1 channel are shown as chemotherapeutics and anti-inflammatory agents.
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