Voltage-Gated Proton Channels
Voltage-gated proton channel (Hv1) mediates robust proton transport along the proton electrochemical gradient. Hv1 is a unique ion channel that is opened by depolarization, but its physiological functions are very sensitive to temperature and pH. Hv1 is mainly expressed in immune cells, including neutrophils and macrophages. In these cells, Hv1 plays a key role in regulating reactive oxygen production and pH homeostasis. Proton transport through Hv1 is regulated by membrane potential and pH differences across cell membranes.
Early research has shown that the properties of Hv1 (including proton conductance and gating) are highly correlated with temperature. Recent findings indicate that Hv1 is highly expressed in metastatic human breast tumor tissues, but not in non-metastatic breast cancer tissues. Having been found highly expressed in other cancer tissues, many scientists wonder the importance of the Hv1 channels in cancer metastasis. Hv1 has recently been characterized in zebrafish, indicating its important role in the immune cells of not only mammals but also non-mammalian vertebrates. A group of small molecule inhibitors of the Hv1 channel is shown as chemotherapeutics and anti-inflammatory drugs.
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