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Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses

Intracellular Cl(−) concentrations ([Cl(−)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(−) is accumulated by the Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1), resulting in a [Cl(−)](i) above electro...

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Autores principales: Schöbel, Nicole, Radtke, Debbie, Lübbert, Matthias, Gisselmann, Günter, Lehmann, Ramona, Cichy, Annika, Schreiner, Benjamin S. P., Altmüller, Janine, Spector, Alan C., Spehr, Jennifer, Hatt, Hanns, Wetzel, Christian H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493563/
https://www.ncbi.nlm.nih.gov/pubmed/23144843
http://dx.doi.org/10.1371/journal.pone.0048005
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author Schöbel, Nicole
Radtke, Debbie
Lübbert, Matthias
Gisselmann, Günter
Lehmann, Ramona
Cichy, Annika
Schreiner, Benjamin S. P.
Altmüller, Janine
Spector, Alan C.
Spehr, Jennifer
Hatt, Hanns
Wetzel, Christian H.
author_facet Schöbel, Nicole
Radtke, Debbie
Lübbert, Matthias
Gisselmann, Günter
Lehmann, Ramona
Cichy, Annika
Schreiner, Benjamin S. P.
Altmüller, Janine
Spector, Alan C.
Spehr, Jennifer
Hatt, Hanns
Wetzel, Christian H.
author_sort Schöbel, Nicole
collection PubMed
description Intracellular Cl(−) concentrations ([Cl(−)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(−) is accumulated by the Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1), resulting in a [Cl(−)](i) above electrochemical equilibrium and a depolarizing Cl(−) efflux upon Cl(−) channel opening. Here, we investigate the [Cl(−)](i) and function of Cl(−) in primary sensory neurons of trigeminal ganglia (TG) of wild type (WT) and NKCC1(−/−) mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(−)](i) of WT TG neurons indicated active NKCC1-dependent Cl(−) accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a reduction of [Cl(−)](i) as well as Ca(2+) transients in a corresponding fraction of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1) were diminished in NKCC1(−/−) TG neurons, but elevated under conditions of a lowered [Cl(−)](o) suggesting a Cl(−)-dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS), we found expression of different Ca(2+)-activated Cl(−) channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(−/−) mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(−)-dependent signal amplification mechanism in TG neurons that requires intracellular Cl(−) accumulation by NKCC1 and the activation of CaCCs.
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spelling pubmed-34935632012-11-09 Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses Schöbel, Nicole Radtke, Debbie Lübbert, Matthias Gisselmann, Günter Lehmann, Ramona Cichy, Annika Schreiner, Benjamin S. P. Altmüller, Janine Spector, Alan C. Spehr, Jennifer Hatt, Hanns Wetzel, Christian H. PLoS One Research Article Intracellular Cl(−) concentrations ([Cl(−)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(−) is accumulated by the Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1), resulting in a [Cl(−)](i) above electrochemical equilibrium and a depolarizing Cl(−) efflux upon Cl(−) channel opening. Here, we investigate the [Cl(−)](i) and function of Cl(−) in primary sensory neurons of trigeminal ganglia (TG) of wild type (WT) and NKCC1(−/−) mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(−)](i) of WT TG neurons indicated active NKCC1-dependent Cl(−) accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a reduction of [Cl(−)](i) as well as Ca(2+) transients in a corresponding fraction of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1) were diminished in NKCC1(−/−) TG neurons, but elevated under conditions of a lowered [Cl(−)](o) suggesting a Cl(−)-dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS), we found expression of different Ca(2+)-activated Cl(−) channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(−/−) mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(−)-dependent signal amplification mechanism in TG neurons that requires intracellular Cl(−) accumulation by NKCC1 and the activation of CaCCs. Public Library of Science 2012-11-08 /pmc/articles/PMC3493563/ /pubmed/23144843 http://dx.doi.org/10.1371/journal.pone.0048005 Text en © 2012 Schöbel et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schöbel, Nicole
Radtke, Debbie
Lübbert, Matthias
Gisselmann, Günter
Lehmann, Ramona
Cichy, Annika
Schreiner, Benjamin S. P.
Altmüller, Janine
Spector, Alan C.
Spehr, Jennifer
Hatt, Hanns
Wetzel, Christian H.
Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title_full Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title_fullStr Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title_full_unstemmed Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title_short Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses
title_sort trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493563/
https://www.ncbi.nlm.nih.gov/pubmed/23144843
http://dx.doi.org/10.1371/journal.pone.0048005
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