Four varieties of voltage-gated proton channels

The properties of voltage-gated proton channels are reviewed, with an emphasis on comparing different cells. Characteristic properties of these unique ion channels are shared by all members of this family. By definition, these channels are voltage-gated, opening upon depolarization of the membrane. Gating is tightly regulated by pHo and pHi resulting in only outward current. H+ channels are inhibited by Cd2+ and Zn2+. Proton channels are extremely selective - no other ions are detectably permeant. H+ currents increase at low pH, but only about two-fold/Unit decrease in pHi. Single channel currents have not been measured, and are likely very small (a few fA). Kinetic properties vary dramatically, suggesting categorization of known H+ channels into four isoforms. Type n channels in snail neurons have extremely rapid gating kinetics, opening and closing in a few milliseconds. Type o channels in newt oocytes and type e in epithelial cells gate more slowly. Type e channels close with a double exponential time course. Type p channels, found mainly in phagocytes, have the slowest gating kinetics, under certain conditions requiring many seconds to open. This tentative classification will evolve, as more information becomes available.