Neuroscience letters, 2004-10, Vol.369 (3), p.250-255
2004
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- Autor(en) / Beteiligte
- Titel
- Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues
- Ist Teil von
- Neuroscience letters, 2004-10, Vol.369 (3), p.250-255
- Ort / Verlag
- Ireland: Elsevier Ireland Ltd
- Erscheinungsjahr
- 2004
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current ( I cap) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I cap was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3940eISSN: 1872-7972DOI: 10.1016/j.neulet.2004.07.059Titel-ID: cdi_crossref_primary_10_1016_j_neulet_2004_07_059
- Format
- –
- Schlagworte
- Animals, Animals, Newborn, Capsaicin, Capsaicin - pharmacology, Cell Line, Chickens, Dorsal root ganglion, Dose-Response Relationship, Drug, Electric Stimulation - methods, Embryo, Mammalian, Embryo, Nonmammalian, Extracellular Space - drug effects, Ganglia, Spinal - cytology, Guinea Pigs, Humans, In Vitro Techniques, Ion Channels - metabolism, Membrane Potentials - drug effects, Membrane Potentials - radiation effects, Models, Molecular, Mutagenesis - physiology, Neurons - drug effects, Oxidation-Reduction - drug effects, Patch-Clamp Techniques - methods, Rabbits, Rats, Receptors, Drug - metabolism, Sequence Alignment - methods, Sulfhydryl Compounds - metabolism, Sulfhydryl oxidation, Swine, Thimerosal, Thimerosal - pharmacology, Transfection, TRPV Cation Channels, TRPV1