Voltage-gated proton channels.

The history of research on voltage-gated proton channels is recounted, from their proposed existence in dinoflagellates by Hastings in 1972 and their demonstration in snail neurons by Thomas and Meech in 1982 to the discovery in 2006 (after a decade of controversy) of genes that unequivocally code for proton channels. Voltage-gated proton channels are perfectly selective for protons, conduct deuterons half as well, and the conductance is strongly temperature dependent. These properties are consistent with a conduction mechanism involving hydrogen-bonded-chain transfer, in which the selectivity filter is a titratable amino acid residue. Channel opening is regulated stringently by pH such that only outward current is normally activated. Main functions of proton channels include acid extrusion from cells and charge compensation for the electrogenic activity of the phagocyte NADPH oxidase. Genetic approaches hold the promise of rapid progress in the near future.