title: The Voltage-Gated Proton Channel: A Riddle, Wrapped in a Mystery, inside an Enigma.
abstract: The main properties of the voltage-gated proton channel (HV1) are described in this review, along with what is known about how the channel protein structure accomplishes its functions. Just as protons are unique among ions, proton channels are unique among ion channels. Their four transmembrane helices sense voltage and the pH gradient and conduct protons exclusively. Selectivity is achieved by the unique ability of H3O(+) to protonate an Asp-Arg salt bridge. Pathognomonic sensitivity of gating to the pH gradient ensures HV1 channel opening only when acid extrusion will result, which is crucial to most of its biological functions. An exception occurs in dinoflagellates in which influx of H(+) through HV1 triggers the bioluminescent flash. Pharmacological interventions that promise to ameliorate cancer, asthma, brain damage in ischemic stroke, Alzheimer's disease, autoimmune diseases, and numerous other conditions await future progress.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush University, 1750 West Harrison, Chicago, Illinois 60612, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: DeCoursey
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D011522:Protons
chemical_list: C510235:HVCN1 protein, human; D007473:Ion Channels; D011522:Protons