Universität zu Köln

Hucho, Tim ORCID: 0000-0002-4147-9308, Suckow, Vanessa, Joseph, Elizabeth K., Kuhn, Julia, Schmoranzer, Jan ORCID: 0000-0002-4482-7080, Dina, Olayinka A., Chen, Xiaojie, Karst, Matthias, Bernateck, Michael, Levine, Jon D. and Ropers, Hans-Hilger (2012). Ca++/CaMKII switches nociceptor-sensitizing stimuli into desensitizing stimuli. J. Neurochem., 123 (4). S. 589 - 602. HOBOKEN: WILEY. ISSN 1471-4159

Full text not available from this repository.

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 (PKCe) 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 PKCe signaling pathway resulted in PKCe translocation. We identified a novel inhibitory cascade to branch off upstream of PKCe, 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED Suckow, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Joseph, Elizabeth K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhn, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmoranzer, Jan UNSPECIFIED orcid.org/0000-0002-4482-7080 UNSPECIFIED Dina, Olayinka A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Xiaojie UNSPECIFIED UNSPECIFIED UNSPECIFIED Karst, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernateck, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Levine, Jon D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ropers, Hans-Hilger UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480258
DOI:	10.1111/j.1471-4159.2012.07920.x
Journal or Publication Title:	J. Neurochem.
Volume:	123
Number:	4
Page Range:	S. 589 - 602
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1471-4159
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-KINASE-C; PKC-EPSILON; MECHANICAL HYPERALGESIA; CAPSAICIN RECEPTOR; SENSORY NEURONS; II-ALPHA; TRPV1; CHANNEL; MEMORY; EPAC Multiple languages Biochemistry & Molecular Biology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48025