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 the flow of io ...

s that have the unique property of opening with

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

, 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 solute concentration across a membrane, and th ...

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

acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

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 (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

s, and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

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 pla ...

. When

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

or other

microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

s are engulfed by phagocytes, the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

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, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(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. As mentioned, 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 Voltage-gated hydrogen channel 1 is a protein that in humans is encoded by the HVCN1 gene. Voltage-gated hydrogen channel 1 is a voltage-gated proton channel that has been shown to allow proton transport into phagosomes and out of many types of ...

References

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