Voltage-gated proton channels are

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s that have the unique property of opening with

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

, but in a strongly pH-sensitive manner. The result is that these channels open only when the

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in Concentration, solute concentration across ...

is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

extrusion from cells. Another important function occurs in

phagocyte Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...

s (e.g.

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

s, and

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s) during the

respiratory burst Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), superoxide anion () and hydrogen peroxide (), from different cell types. This is usually utilised for mammalian immunological defence, but also pl ...

. When

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

or other

microbe A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

s are engulfed by phagocytes, the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

NADPH oxidase NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...

assembles in the membrane and begins to produce

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(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. The functional expression of Hv1 in phagocytes has been well characterized in mammals, and recently in zebrafish, suggesting its important roles in the immune cells of mammals and non-mammalian vertebrates. A group of small molecule inhibitors of the Hv1 channel are shown as chemotherapeutics and anti-inflammatory agents. When activated, the voltage-gated proton channel Hv1 can allow up to 100,000 hydrogen ions across the membrane each second. Whereas most voltage-gated ion channels contain a central pore that is surrounding by alpha helices and the voltage-sensing domain (VSD), voltage-gated hydrogen channels contain no central pore, so their voltage-sensing regions (VSD) carry out the job of bringing acidic protons across the membrane. Because the relative H+ concentrations on each side of the membrane result in a pH gradient, these voltage-gated hydrogen channels only carry outward current, meaning they are used to move acidic protons out of the membrane. As a result, the opening of voltage-gated hydrogen channels usually hyperpolarize the cell membrane, or makes the membrane potential more negative. A recent discovery has shown that the voltage-gated proton channel Hv1 is highly expressed in human breast tumor tissues that are metastatic, but not in non-metastatic breast cancer tissues. Because it has also been found to be highly expressed in other cancer tissues, the study of the voltage-gated proton channel has led many scientists to wonder what its importance is in cancer metastasis. However, much is still being discovered concerning the structure and function of the voltage-gated proton channel.

Known types

* HVCN1

References

{{Ion channels, g4 Ion channels Immunology Voltage-gated ion channels