Voltage gated proton channels were first discovered in snail neurons and recently have been found in many mammalian cells. As their name suggests, H⁺ channels are sensitive to voltage, with an open probability that increases with membrane depolarization. Many properties that are shared by voltage-gated proton channels make them unique among ion channels. They show high selectivity for protons, strongly pH dependent gating, and a tiny single channel conductance. Although they are inhibited by divalent cations, including zinc and cadmium, no effective blockers exist. There is sufficient evidence to suggest that they are not water filled pores, unlike many other membrane bound ion channels. Instead, protons probably are conducted by a "hydrogen bonded chain" mechanism that resembles the Grotthuss mechanism in water. Differences in activation and deactivation kinetics of H⁺ currents in different cells suggest that there may be at least 4 isoforms of voltage gated proton channels. Gating kinetics may reflect specific functions. Voltage gated proton channels are well suited to extrude acid from cells and also may function in the extrusion of metabolic acid in the form of CO₂ from the lungs. The best established function of H⁺ channels is in mammalian phagocytes, where they extrude protons to compensate for the charge separation created by the movement of electrons across the membrane by the bactericidal enzyme NADPH oxidase.