Schoebel, Nicole, Radtke, Debbie, Luebbert, Matthias, Gisselmann, Guenter, Lehmann, Ramona, Cichy, Annika ORCID: 0000-0002-4620-7854, Schreiner, Benjamin S. P., Altmueller, Janine, Spector, Alan C., Spehr, Jennifer, Hatt, Hanns and Wetzel, Christian H. (2012). Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses. PLoS One, 7 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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 Ca2+ transients in a corresponding fraction of TG neurons. Ca2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca2+ channels (VGCCs). Ca2+ 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 Ca2(+-)activated Cl- channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca2+ 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 Ca2+-activated Cl--dependent signal amplification mechanism in TG neurons that requires intracellular Cl- accumulation by NKCC1 and the activation of CaCCs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schoebel, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radtke, DebbieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luebbert, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gisselmann, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, RamonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichy, AnnikaUNSPECIFIEDorcid.org/0000-0002-4620-7854UNSPECIFIED
Schreiner, Benjamin S. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spector, Alan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spehr, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hatt, HannsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wetzel, Christian H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-479062
DOI: 10.1371/journal.pone.0048005
Journal or Publication Title: PLoS One
Volume: 7
Number: 11
Date: 2012
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OLFACTORY SENSORY NEURONS; CA2+-ACTIVATED CL-CHANNELS; DORSAL-ROOT; NA-K-2CL COTRANSPORTER; IN-VITRO; NA+-K+-2CL(-) COTRANSPORTER; SOMATOSENSORY SYSTEM; NKCC1 COTRANSPORTER; RECEPTOR-CELLS; PAIN PATHWAYMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47906

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