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  Ca++/CaMKII switches nociceptor-sensitizing stimuli into desensitizing stimuli

Hucho, T., Suckow, V., Joseph, E. K., Kuhn, J., Schmoranzer, J., Dina, O. A., et al. (2012). Ca++/CaMKII switches nociceptor-sensitizing stimuli into desensitizing stimuli. Journal of Neurochemistry: official journal of the International Society for Neurochemistry, 123(4), 589-601. doi:10.1111/j.1471-4159.2012.07920.x.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC70-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC71-0
Genre: Journal Article

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© 2012 The Authors © 2012 International Society for Neurochemistry
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 Creators:
Hucho, T.1, Author              
Suckow, V.1, Author              
Joseph, E. K., Author
Kuhn, J., Author
Schmoranzer, J., Author
Dina, O. A., Author
Chen, X., Author
Karst, M., Author
Bernateck, M., Author
Levine, J. D., Author
Ropers, H.-H.2, Author              
Affiliations:
1Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479646              
2Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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Free keywords: Adrenergic beta-Agonists/pharmacology Analysis of Variance Animals Calcium/*metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism Cells, Cultured Cyclic AMP/analogs & derivatives/pharmacology Electric Stimulation Enzyme Inhibitors/pharmacology Ganglia, Spinal/cytology Hyperalgesia/drug therapy/physiopathology Inositol 1,4,5-Trisphosphate/pharmacology Isoproterenol/pharmacology Male Nerve Fibers/drug effects/physiology Neurons/drug effects/*metabolism Nociceptors/*physiology Pain Threshold/drug effects/*physiology Protein Kinase C-epsilon/metabolism Protein Transport/drug effects Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled/metabolism Ryanodine/pharmacology Signal Transduction/drug effects/physiology TRPV Cation Channels/metabolism Thionucleotides/pharmacology Uridine Triphosphate/pharmacology
 Abstract: Many extracellular factors sensitize nociceptors. Often they act simultaneously and/or sequentially on nociceptive neurons. We investigated if stimulation of the protein kinase C epsilon (PKCepsilon) signaling pathway influences the signaling of a subsequent sensitizing stimulus. Central in activation of PKCs is their transient translocation to cellular membranes. We found in cultured nociceptive neurons that only a first stimulation of the PKCepsilon signaling pathway resulted in PKCepsilon translocation. We identified a novel inhibitory cascade to branch off upstream of PKCepsilon, but downstream of Epac via IP3-induced calcium release. This signaling branch actively inhibited subsequent translocation and even attenuated ongoing translocation. A second 'sensitizing' stimulus was rerouted from the sensitizing to the inhibitory branch of the signaling cascade. Central for the rerouting was cytoplasmic calcium increase and CaMKII activation. Accordingly, in behavioral experiments, activation of calcium stores switched sensitizing substances into desensitizing substances in a CaMKII-dependent manner. This mechanism was also observed by in vivo C-fiber electrophysiology corroborating the peripheral location of the switch. Thus, we conclude that the net effect of signaling in nociceptors is defined by the context of the individual cell's signaling history.

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Language(s): eng - English
 Dates: 2012-09-282012-11
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1111/j.1471-4159.2012.07920.x
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Title: Journal of Neurochemistry : official journal of the International Society for Neurochemistry
  Other : J. Neurochem.
Source Genre: Journal
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Publ. Info: New York : Raven Press [etc.]
Pages: - Volume / Issue: 123 (4) Sequence Number: - Start / End Page: 589 - 601 Identifier: ISSN: 0022-3042
CoNE: /journals/resource/954925416956