PMID- 23144843
OWN - NLM
STAT- MEDLINE
DCOM- 20130425
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Trigeminal ganglion neurons of mice show intracellular chloride accumulation and 
      chloride-dependent amplification of capsaicin-induced responses.
PG  - e48005
LID - 10.1371/journal.pone.0048005 [doi]
LID - e48005
AB  - 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.
FAU - Schobel, Nicole
AU  - Schobel N
AD  - Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany. 
      nicole.schoebel@gmx.de
FAU - Radtke, Debbie
AU  - Radtke D
FAU - Lubbert, Matthias
AU  - Lubbert M
FAU - Gisselmann, Gunter
AU  - Gisselmann G
FAU - Lehmann, Ramona
AU  - Lehmann R
FAU - Cichy, Annika
AU  - Cichy A
FAU - Schreiner, Benjamin S P
AU  - Schreiner BS
FAU - Altmuller, Janine
AU  - Altmuller J
FAU - Spector, Alan C
AU  - Spector AC
FAU - Spehr, Jennifer
AU  - Spehr J
FAU - Hatt, Hanns
AU  - Hatt H
FAU - Wetzel, Christian H
AU  - Wetzel CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121108
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calcium Channel Agonists)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chloride Channels)
RN  - 0 (Chlorides)
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (Pyridazines)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (SLC12A2 protein, human)
RN  - 0 (Slc12a2 protein, mouse)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 99460MG420 (gabazine)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Calcium Channel Agonists/pharmacology
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Signaling
MH  - Capsaicin/*pharmacology
MH  - Cells, Cultured
MH  - Chloride Channels/genetics/metabolism
MH  - Chlorides/*metabolism/physiology
MH  - Female
MH  - GABA-A Receptor Antagonists/pharmacology
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Membrane Potentials
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/drug effects/*metabolism
MH  - Primary Cell Culture
MH  - Pyridazines/pharmacology
MH  - Receptors, GABA-A/metabolism
MH  - Sodium-Potassium-Chloride Symporters/genetics/metabolism
MH  - Solute Carrier Family 12, Member 2
MH  - Synaptic Transmission
MH  - TRPV Cation Channels/genetics/metabolism
MH  - Transcriptome
MH  - Trigeminal Ganglion/*cytology/drug effects
PMC - PMC3493563
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/11/13 06:00
MHDA- 2013/04/26 06:00
PMCR- 2012/11/08
CRDT- 2012/11/13 06:00
PHST- 2012/08/03 00:00 [received]
PHST- 2012/09/19 00:00 [accepted]
PHST- 2012/11/13 06:00 [entrez]
PHST- 2012/11/13 06:00 [pubmed]
PHST- 2013/04/26 06:00 [medline]
PHST- 2012/11/08 00:00 [pmc-release]
AID - PONE-D-12-23174 [pii]
AID - 10.1371/journal.pone.0048005 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e48005. doi: 10.1371/journal.pone.0048005. Epub 2012 Nov 8.