title: Proton block of proton-activated TRPV1 current.
abstract: The TRPV1 cation channel is a polymodal nociceptor that is activated by heat and ligands such as capsaicin and is highly sensitive to changes in extracellular pH. In the body core, where temperature is usually stable and capsaicin is normally absent, H(+) released in response to ischemia, tissue injury, or inflammation is the best-known endogenous TRPV1 agonist, activating the channel to mediate pain and vasodilation. Paradoxically, removal of H(+) elicits a transient increase in TRPV1 current that is much larger than the initial H(+)-activated current. We found that this prominent OFF response is caused by rapid recovery from H(+) inhibition of the excitatory current carried by H(+)-activated TRPV1 channels. H(+) inhibited current by interfering with ion permeation. The degree of inhibition is voltage and permeant ion dependent, and it can be affected but not eliminated by mutations to acidic residues within or near the ion selectivity filter. The opposing H(+)-mediated gating and permeation effects produce complex current responses under different cellular conditions that are expected to greatly affect the response of nociceptive neurons and other TRPV1-expressing cells.
authors.affiliation: Department of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA 95616.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA 95616 jzheng@ucdavis.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011522:Protons; D050916:TRPV Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011522:Protons; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse