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Molecular Pain

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Open Access 01-12-2009 | Research

PKCε-dependent potentiation of TTX-resistant Na_v1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons

Authors: Chun-Lei Cang, Hua Zhang, Yu-Qiu Zhang, Zhi-Qi Zhao

Published in: Molecular Pain | Issue 1/2009

Abstract

Background

Substance P (SP), which mainly exists in a subtype of small-diameter dorsal root ganglion (DRG) neurons, is an important signal molecule in pain processing in the spinal cord. Our previous results have proved the expression of SP receptor neurokinin-1 (NK-1) on DRG neurons and its interaction with transient receptor potential vanilloid 1 (TRPV1) receptor.

Results

In this study we investigated the effect of NK-1 receptor agonist on Na_v1.8, a tetrodotoxin (TTX)-resistant sodium channel, in rat small-diameter DRG neurons employing whole-cell patch clamp recordings. NK-1 agonist [Sar⁹, Met(O₂)¹¹]-substance P (Sar-SP) significantly enhanced the Na_v1.8 currents in a subgroup of small-diameter DRG neurons under both the normal and inflammatory situation, and the enhancement was blocked by NK-1 antagonist Win51708 and protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM), but not the protein kinase A (PKA) inhibitor H89. In particular, the inhibitor of PKCε, a PKC isoform, completely blocked this effect. Under current clamp model, Sar-SP reduced the amount of current required to evoke action potentials and increased the firing rate in a subgroup of DRG neurons.

Conclusion

These data suggest that activation of NK-1 receptor potentiates Na_v1.8 sodium current via PKCε-dependent signaling pathway, probably participating in the generation of inflammatory hyperalgesia.

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Title: PKCε-dependent potentiation of TTX-resistant Nav1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons
Authors: Chun-Lei Cang
Hua Zhang
Yu-Qiu Zhang
Zhi-Qi Zhao
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-5-33

At a glance: The STEP trials

Springer Medicine

PKCε-dependent potentiation of TTX-resistant Na_v1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons

Abstract

Background

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusion

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