Voltage‐Gated Proton Channels

Abstract

Voltage‐gated proton channels, H V 1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely, the mechanism by which voltage‐dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage‐sensing domain of most other voltage‐gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single‐channel conductance approximately 10 3 times smaller than most ion channels, voltage‐dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn 2+ (in many species) but an absence of other potent inhibitors. The recent identification of H V 1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH‐dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B‐cell receptor mediated responses in B‐lymphocytes. The most elaborate and best‐established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by H V 1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H + for the production of H 2 O 2 and HOCl, reactive oxygen species crucial to killing pathogens. © 2012 American Physiological Society. Compr Physiol 2:1355‐1385, 2012.

Asynchronous Ca 2 + current conducted by voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels and its implications for asynchronous neurotransmitter release

“…2 A-D) nor lowering the pH of the extracellular or intracellular solution (Fig. 2 E-H) altered I Async , eliminating contributions from Ca 2+ -activated Cl − channels (18) and voltage-gated proton channels (19) to I Async . Replacing Tris + in the extracellular medium with Na + and K + had no effect (Fig.…”

Proton channels and renal hypertensive injury: a key piece of the Dahl salt-sensitive rat puzzle?

“…Voltage-gated proton channels (encoded Hvcn1 in humans) are ion channels that mediate acid extrusion from cells (8). Although the existence of proton channels has been recognized for some time (71), the genes encoding Hv1 were not identified until 2006 (25,62,66). Despite this, much is known regarding the biophysical properties and function of proton channels in mammalian species.…”

“…Despite this, much is known regarding the biophysical properties and function of proton channels in mammalian species. As their name suggests, voltage-gated proton channels are voltage-sensitive, opening in response to membrane depolarization (25). The opening threshold for voltage-gated proton channels is 20 mV positive, far from the resting potential of most cells at around 60 mV negative (25).…”

Acidification of the intimal fluid: the perfect storm for atherogenesis

“…Thus, macrophages, the most abundant immune cells in atherosclerotic lesions, will remain viable despite the acidic microenvironment of the atherosclerotic intima and are subject to acidosis-induced a key bactericidal response, the oxidative burst ( 16,17 ). Acidosis greatly enhances the receptor-mediated uptake of opsonized bacteria into macrophages thereby promoting effi cient clearance of an infection ( 18 ), and it also boosts antigen presentation by these cells via enhancing fl uidphase endocytosis and increasing the expression of molecules involved in antigen presentation ( 19,20 ).…”