Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schoebel, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Radtke, Debbie UNSPECIFIED UNSPECIFIED UNSPECIFIED Luebbert, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Gisselmann, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Ramona UNSPECIFIED UNSPECIFIED UNSPECIFIED Cichy, Annika UNSPECIFIED orcid.org/0000-0002-4620-7854 UNSPECIFIED Schreiner, Benjamin S. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Spector, Alan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Spehr, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatt, Hanns UNSPECIFIED UNSPECIFIED UNSPECIFIED Wetzel, Christian H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language 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 Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47906