TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons

dc.contributor.authorEberhardt, Mirjam
dc.contributor.authorStueber, Thomas
dc.contributor.authorde la Roche, Jeanne
dc.contributor.authorHerzog, Christine
dc.contributor.authorLeffler, Andreas
dc.contributor.authorReeh, Peter W.
dc.contributor.authorKistner, Katrin
dc.date.accessioned2017-12-19
dc.date.available2017-12-04
dc.date.created2017
dc.date.issued2017-12-19
dc.description.abstractBackground Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. Methods Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death. Release of calcitonin gene-related peptide (CGRP) from isolated mouse peripheral nerves was determined with ELISA. Results Lidocaine up to 10 mM induced a concentration-dependent reversible increase in intracellular Ca2+ in DRG neurons from wildtype and mutant mice lacking one of the two receptors, but not in neurons lacking both TRPA1 and TRPV1. 30 mM lidocaine also released Ca2+ from intracellular stores, presumably from the endoplasmic reticulum. While 10 mM lidocaine evoked an axonal CGRP release requiring expression of either TRPA1 or TRPV1, CGRP release induced by 30 mM lidocaine again mobilized internal Ca2+ stores. Lidocaine-evoked cell death required neither TRPV1 nor TRPA1. Summary Depending on the concentration, lidocaine employs TRPV1, TRPA1 and intracellular Ca2+ stores to induce a Ca2+-dependent release of the neuropeptide CGRP. Lidocaine-evoked cell death does not seem to require Ca2+ influx through TRPV1 or TRPV1.en
dc.identifier.citationPLoS ONE 12.11 (2017). <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188008>
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0188008
dc.identifier.opus-id9031
dc.identifier.urihttps://open.fau.de/handle/openfau/9031
dc.identifier.urnurn:nbn:de:bvb:29-opus4-90316
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectNeurons
dc.subjectNeuronal death
dc.subjectCell death
dc.subjectApoptosis
dc.subjectCell staining
dc.subjectCytotoxicity
dc.subjectSensory neurons
dc.subjectHEK 293 cells
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleTRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neuronsen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.issue11
local.journal.titlePLoS ONE
local.journal.volume12
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2018
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