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TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons.
PLoS One. 2017; 12(11):e0188008.Plos

Abstract

BACKGROUND

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.

Authors+Show Affiliations

Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany. Department for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.Department for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.Department for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany. Institute of Neurophysiology, Hannover Medical School, Hannover, Germany.Department for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.Department for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany.Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29141003

Citation

Eberhardt, Mirjam, et al. "TRPA1 and TRPV1 Are Required for Lidocaine-evoked Calcium Influx and Neuropeptide Release but Not Cytotoxicity in Mouse Sensory Neurons." PloS One, vol. 12, no. 11, 2017, pp. e0188008.
Eberhardt M, Stueber T, de la Roche J, et al. TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons. PLoS One. 2017;12(11):e0188008.
Eberhardt, M., Stueber, T., de la Roche, J., Herzog, C., Leffler, A., Reeh, P. W., & Kistner, K. (2017). TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons. PloS One, 12(11), e0188008. https://doi.org/10.1371/journal.pone.0188008
Eberhardt M, et al. TRPA1 and TRPV1 Are Required for Lidocaine-evoked Calcium Influx and Neuropeptide Release but Not Cytotoxicity in Mouse Sensory Neurons. PLoS One. 2017;12(11):e0188008. PubMed PMID: 29141003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons. AU - Eberhardt,Mirjam, AU - Stueber,Thomas, AU - de la Roche,Jeanne, AU - Herzog,Christine, AU - Leffler,Andreas, AU - Reeh,Peter W, AU - Kistner,Katrin, Y1 - 2017/11/15/ PY - 2017/05/05/received PY - 2017/10/29/accepted PY - 2017/11/16/entrez PY - 2017/11/16/pubmed PY - 2017/12/27/medline SP - e0188008 EP - e0188008 JF - PloS one JO - PLoS One VL - 12 IS - 11 N2 - BACKGROUND: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29141003/TRPA1_and_TRPV1_are_required_for_lidocaine_evoked_calcium_influx_and_neuropeptide_release_but_not_cytotoxicity_in_mouse_sensory_neurons_ L2 - https://dx.plos.org/10.1371/journal.pone.0188008 DB - PRIME DP - Unbound Medicine ER -