Hauptseite > Publikationsdatenbank > Modulation of chloride homeostasis by inflammatory mediators in dorsal root ganglion neurons > print

001     238
005     20200402205327.0
024 7 _ |2 pmid
|a pmid:18700020
024 7 _ |2 pmc
|a pmc:PMC2526990
024 7 _ |2 DOI
|a 10.1186/1744-8069-4-32
024 7 _ |2 WOS
|a WOS:000258959400001
037 _ _ |a PreJuSER-238
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Neurosciences
100 1 _ |0 P:(DE-HGF)0
|a Funk, K.
|b 0
245 _ _ |a Modulation of chloride homeostasis by inflammatory mediators in dorsal root ganglion neurons
260 _ _ |a London
|b BioMed Central
|c 2008
300 _ _ |a 32 - 43
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 19121
|a Molecular Pain
|v 4
|x 1744-8069
500 _ _ |a This work was supported by the Deutsche Forschungsgemeinschaft (Fr 937/6).
520 _ _ |a Chloride currents in peripheral nociceptive neurons have been implicated in the generation of afferent nociceptive signals, as Cl- accumulation in sensory endings establishes the driving force for depolarizing, and even excitatory, Cl- currents. The intracellular Cl- concentration can, however, vary considerably between individual DRG neurons. This raises the question, whether the contribution of Cl- currents to signal generation differs between individual afferent neurons, and whether the specific Cl- levels in these neurons are subject to modulation. Based on the hypothesis that modulation of the peripheral Cl- homeostasis is involved in the generation of inflammatory hyperalgesia, we examined the effects of inflammatory mediators on intracellular Cl- concentrations and on the expression levels of Cl- transporters in rat DRG neurons.We developed an in vitro assay for testing how inflammatory mediators influence Cl- concentration and the expression of Cl- transporters. Intact DRGs were treated with 100 ng/ml NGF, 1.8 microM ATP, 0.9 microM bradykinin, and 1.4 microM PGE2 for 1-3 hours. Two-photon fluorescence lifetime imaging with the Cl--sensitive dye MQAE revealed an increase of the intracellular Cl- concentration within 2 hours of treatment. This effect coincided with enhanced phosphorylation of the Na+-K+-2Cl- cotransporter NKCC1, suggesting that an increased activity of that transporter caused the early rise of intracellular Cl- levels. Immunohistochemistry of NKCC1 and KCC2, the main neuronal Cl- importer and exporter, respectively, exposed an inverse regulation by the inflammatory mediators. While the NKCC1 immunosignal increased, that of KCC2 declined after 3 hours of treatment. In contrast, the mRNA levels of the two transporters did not change markedly during this time. These data demonstrate a fundamental transition in Cl- homeostasis toward a state of augmented Cl- accumulation, which is induced by a 1-3 hour treatment with inflammatory mediators.Our findings indicate that inflammatory mediators impact on Cl- homeostasis in DRG neurons. Inflammatory mediators raise intracellular Cl- levels and, hence, the driving force for depolarizing Cl- efflux. These findings corroborate current concepts for the role of Cl- regulation in the generation of inflammatory hyperalgesia and allodynia. As the intracellular Cl- concentration rises in DRG neurons, afferent signals can be boosted by excitatory Cl- currents in the presynaptic terminals. Moreover, excitatory Cl- currents in peripheral sensory endings may also contribute to the generation or modulation of afferent signals, especially in inflamed tissue.
536 _ _ |0 G:(DE-Juel1)FUEK409
|2 G:(DE-HGF)
|a Funktion und Dysfunktion des Nervensystems
|c P33
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Adenosine Triphosphate: pharmacology
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Bradykinin: pharmacology
650 _ 2 |2 MeSH
|a Chlorides: metabolism
650 _ 2 |2 MeSH
|a Dinoprostone: pharmacology
650 _ 2 |2 MeSH
|a Ganglia, Spinal: cytology
650 _ 2 |2 MeSH
|a Ganglia, Spinal: drug effects
650 _ 2 |2 MeSH
|a Ganglia, Spinal: metabolism
650 _ 2 |2 MeSH
|a Homeostasis: drug effects
650 _ 2 |2 MeSH
|a Homeostasis: physiology
650 _ 2 |2 MeSH
|a Inflammation Mediators: pharmacology
650 _ 2 |2 MeSH
|a Nerve Growth Factors: pharmacology
650 _ 2 |2 MeSH
|a Neurons: drug effects
650 _ 2 |2 MeSH
|a Neurons: metabolism
650 _ 2 |2 MeSH
|a Organ Culture Techniques
650 _ 2 |2 MeSH
|a Rats
650 _ 7 |0 0
|2 NLM Chemicals
|a Chlorides
650 _ 7 |0 0
|2 NLM Chemicals
|a Inflammation Mediators
650 _ 7 |0 0
|2 NLM Chemicals
|a Nerve Growth Factors
650 _ 7 |0 363-24-6
|2 NLM Chemicals
|a Dinoprostone
650 _ 7 |0 56-65-5
|2 NLM Chemicals
|a Adenosine Triphosphate
650 _ 7 |0 58-82-2
|2 NLM Chemicals
|a Bradykinin
650 _ 7 |2 WoSType
|a J
700 1 _ |0 P:(DE-HGF)0
|a Woitecki, A.
|b 1
700 1 _ |0 P:(DE-HGF)0
|a Franjic-Würtz, C.
|b 2
700 1 _ |0 P:(DE-Juel1)131924
|a Gensch, T.
|b 3
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Möhrlen, F.
|b 4
700 1 _ |0 P:(DE-HGF)0
|a Frings, S.
|b 5
773 _ _ |0 PERI:(DE-600)2174252-2
|a 10.1186/1744-8069-4-32
|g Vol. 4, p. 32 - 43
|p 32 - 43
|q 4<32 - 43
|t Molecular pain
|v 4
|x 1744-8069
|y 2008
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526990
909 C O |o oai:juser.fz-juelich.de:238
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914 1 _ |y 2008
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |0 I:(DE-Juel1)VDB804
|d 31.12.2008
|g INB
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|l Zelluläre Biophysik
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981 _ _ |a I:(DE-Juel1)IBI-1-20200312
981 _ _ |a I:(DE-Juel1)ICS-4-20110106

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