Schoebel, Nicole and Radtke, Debbie and Luebbert, Matthias and Gisselmann, Guenter and Lehmann, Ramona and Cichy, Annika and Schreiner, Benjamin S. P. and Altmueller, Janine and Spector, Alan C. and Spehr, Jennifer and 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): e48005. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | 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 PATHWAY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 08:14 |
| Last Modified: | 04 May 2020 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17813 |
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