TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons
| Autor: | Eberhardt, Mirjam, Stueber, Thomas, de la Roche, Jeanne, Herzog, Christine, Leffler, Andreas, Reeh, Peter W., Kistner, Katrin |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Patch-Clamp Techniques Sensory Receptor Cells Cytotoxicity Calcitonin Gene-Related Peptide lcsh:Medicine TRPV Cation Channels Apoptosis Research and Analysis Methods Toxicology Pathology and Laboratory Medicine Mice Medizinische Fakultät Animal Cells Ganglia Spinal Medicine and Health Sciences Animals ddc:610 lcsh:Science TRPA1 Cation Channel Cells Cultured Neurons Staining Mice Knockout Neuronal Death Ion Transport Cell Death lcsh:R HEK 293 cells Biology and Life Sciences Cell Staining Lidocaine Cell Biology nervous system Cell Processes Specimen Preparation and Treatment Cellular Neuroscience Cell lines lcsh:Q Sensory Neurons Calcium Female Cellular Types Biological cultures psychological phenomena and processes Research Article Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 11, p e0188008 (2017) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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