Voltage-gated proton channel

Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner.[1] The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.[2]

Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, and macrophages) during the respiratory burst. When bacteria or other microbes are engulfed by phagocytes, the enzyme NADPH oxidase assembles in the membrane and begins to produce reactive oxygen species (ROS) that help kill bacteria.[3] NADPH oxidase is electrogenic,[4] moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.[5] A group of small molecule inhibitors of the Hv1 channel are shown as chemotherapeutics and anti-inflammatory agents.[6]

Known types

References

  1. ↑ Cherny, V.V.; Markin, V.S.; DeCoursey, T.E. (1995), "The voltage-activated hydrogen ion conductance in rat alveolar epithelial cells is determined by the pH gradient", Journal of General Physiology (June 1995) 105 (6): 861–896, doi:10.1085/jgp.105.6.861, retrieved 2008-07-14
  2. ↑ DeCoursey, T.E. (2003), "Voltage-gated proton channels and other proton transfer pathways", Physiological Reviews 83 (2): 475–579, doi:10.1152/physrev.00028.2002 (inactive 2015-02-01), OCLC 205658168, PMID 12663866, retrieved 2008-07-14
  3. ↑ Babior, B.M. (1999-03-01), "NADPH Oxidase: An Update.", Blood 93 (5): 1464–1476, ISSN 1528-0020, retrieved 2008-07-14
  4. ↑ Henderson, L.M.; Chappell, J.B.; Jones, O.T.G. (1987-09-01), "The superoxide-generating NADPH oxidase of human neutrophils is electrogenic and associated with an H+ channel", The Biochemical Journal 246 (2): 325–329, ISSN 0264-6021, OCLC 116254550, retrieved 2008-07-14
  5. ↑ Murphy, R.; DeCoursey, T.E. (2006), "Charge compensation during the phagocyte respiratory burst", Biochimica et Biophysica Acta, Bioenergetics (2006-08-08) 1757 (8): 996–1011, doi:10.1016/j.bbabio.2006.01.005, PMID 16483534
  6. ↑ Hong, L; Pathak, M. M.; Kim, I. H.; Ta, D; Tombola, F (2013). "Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains". Neuron 77 (2): 274–87. doi:10.1016/j.neuron.2012.11.013. PMC 3559007. PMID 23352164.