Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition

Vetter, Irina, Hein, Alexander, Sattler, Simon, Hessler, Sabine, Touska, Filip, Bressan, Elisangela, Parra, Andres, Hager, Ulrich, Leffler, Andreas, Boukalova, Stepana, Nissen, Matthias, Lewis, Richard J., Belmonte, Carlos, Alzheimer, Christian, Huth, Tobias, Vlachova, Viktorie, Reeh, Peter W. and Zimmermann, Katharina (2013) Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition. Journal of Neuroscience, 33 42: 16627-16641. doi:10.1523/JNEUROSCI.1473-13.2013

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Author Vetter, Irina
Hein, Alexander
Sattler, Simon
Hessler, Sabine
Touska, Filip
Bressan, Elisangela
Parra, Andres
Hager, Ulrich
Leffler, Andreas
Boukalova, Stepana
Nissen, Matthias
Lewis, Richard J.
Belmonte, Carlos
Alzheimer, Christian
Huth, Tobias
Vlachova, Viktorie
Reeh, Peter W.
Zimmermann, Katharina
Title Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.1473-13.2013
Open Access Status File (Publisher version)
Volume 33
Issue 42
Start page 16627
End page 16641
Total pages 15
Place of publication London, United Kingdom
Publisher Informa Healthcare
Language eng
Abstract Topically applied camphor elicits a sensation of cool, but nothing is known about how it affects cold temperature sensing. We found that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to cold, but desensitizes and partially blocks heterologously expressed TRPM8(transient receptor potential cation channel subfamily M member 8). In contrast, camphor reduces potassium outward currents in cultured sensory neurons and, in cold nociceptors, the cold-sensitizing effects of camphor and menthol are additive. Using a membrane potential dye-based screening assay and heterologously expressed potassium channels, we found that the effects of camphor are mediated by inhibition of K(v)7.2/3 channels subtypes that generate the M-current in neurons. In line with this finding, the specific M-current blocker XE991 reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M-channel blocking effects of XE991 and camphor are not sufficient to initiate cold transduction but require a cold-activated inward current generated by TRPM8. The cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold nociceptors. Low-threshold corneal cold thermoreceptors that express high levels of TRPM8 and lack potassium channels are not affected by camphor. We also found that menthol-like camphor-potently inhibits K(v)7.2/3 channels. The apparent functional synergism arising from TRPM8 activation and M-current block can improve the effectiveness of topical coolants and cooling lotions, and may also enhance TRPM8-mediated analgesia.
Keyword Root Ganglion Neurons
Sensory Neurons
Trp Channels
Potassium Channels
Pain Pathways
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID Zi1172/1-1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
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