The contribution of TRPM8 channels to cold sensing in mammalian neurones

Peña, Elvira de la; Mälkiä, Annika; Cabedo, Hugo; Belmonte, Carlos; Viana, Félix

doi:10.1113/jphysiol.2005.086546

Cited by 69 publications

(52 citation statements)

References 48 publications

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“…Rat TRPM8 cDNA (a gift from Dr. David Julius, University of California, San Francisco, CA) was subcloned in the bicistronic vector pcINeo/internal ribosomal entry site-green fluorescent protein (GFP), as described previously, and used for transient transfection in HEK293 cells (de la Pena et al, 2005). Mouse ankyrin-repeat TRP subtype 1 (TRPA1) in pCDNA5 (a gift from Dr. Ardem Patapoutian, Scripps Research Institute, La Jolla, CA) was cotransfected with pGreen Lantern-1 GFP (Invitrogen, Carlsbad, CA)at a 1:1 ratio.…”

Section: Methodsmentioning

confidence: 99%

“…ϩ cultured trigeminal ganglion neurons was much lower than that of hippocampal neurons transiently transfected with recombinant TRPM8 channels (de la Pena et al, 2005) and hypothesized that TRPM8 channels could be modulated intrinsically to shift their activation threshold. Thus far, very little is known about sensitizing agents of native TRPM8 channels.…”

Section: Specific Effects Of Bctc On Trpm8 Channelsmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Madrid¹,

Donovan-Rodríguez²,

Meseguer³

et al. 2006

J. Neurosci.

153

161

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Transient receptor potential melastatin 8 (TRPM8) is the best molecular candidate for innocuous cold detection by peripheral thermoreceptor terminals. To dissect out the contribution of this cold-and menthol-gated, nonselective cation channel to cold transduction, we identified BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide] as a potent and full blocker of recombinant TRPM8 channels. In cold-sensitive trigeminal ganglion neurons of mice and guinea pig, responses to menthol were abolished by BCTC. In contrast, the effect of BCTC on cold-evoked responses was variable but showed a good correlation with the presence or lack of menthol sensitivity in the same neuron, suggesting a specific blocking action of BCTC on TRPM8 channels. The biophysical properties of native cold-gated currents (I cold ), and the currents blocked by BCTC were nearly identical, consistent with a role of this channel in cold sensing at the soma. The temperature activation threshold of native TRPM8 channels was significantly warmer than those reported in previous expression studies. The effect of BCTC on native I cold was characterized by a dose-dependent shift in the temperature threshold of activation.The role of TRPM8 in transduction was further investigated in the guinea pig cornea, a peripheral territory densely innervated with cold thermoreceptors. All cold-sensitive terminals were activated by menthol, suggesting the functional expression of TRPM8 channels in their membrane. However, the spontaneous activity and firing pattern characteristic of cold thermoreceptors was totally immune to TRPM8 channel blockade with BCTC or SKF96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1 H-imidazole hydrochloride). Cold-evoked responses in corneal terminals were also essentially unaffected by these drugs, whereas responses to menthol were completely abolished. The minor impairment in the ability to transduce cold stimuli by peripheral corneal thermoreceptors during TRPM8 blockade unveils an overlapping functional role for various thermosensitive mechanisms in these nerve terminals.

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Section: Methodsmentioning

confidence: 99%

Section: Specific Effects Of Bctc On Trpm8 Channelsmentioning

confidence: 99%

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Madrid¹,

Donovan-Rodríguez²,

Meseguer³

et al. 2006

J. Neurosci.

153

161

View full text Add to dashboard Cite

show abstract

“…The recent identification of the TRPM8 (8,9) and TRPA1 (10) as putative cold -responsive thermoreceptors offers a mechanism where cold thermal stimulation may directly initiate nerve activity. Although further studies have questioned the role of TRPA1 in cold sensation (11), TRPM8 expressing neurons are responsive to cold (12,13), whereas their contribution to cold-induced hyperalgesia is unknown. The application of a cold stimulus to teeth with irreversible pulpitis may produce a long-lasting pain response and a change in the expression of cold thermoreceptors may be associated with this response.…”

Section: Introductionmentioning

confidence: 99%

TRPM8 Axonal Expression is Decreased in Painful Human Teeth with Irreversible Pulpitis and Cold Hyperalgesia

Alvarado¹,

Perry²,

Hargreaves³

et al. 2007

Journal of Endodontics

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Pulpitis pain may be triggered by a cold stimulus, yet the cellular mechanisms responsible for this phenomenon are largely unknown. One possible mechanism involves the direct activation of coldresponsive thermoreceptors. The purpose of this study was to evaluate the possible role of the TRPM8 thermoreceptor in cold-mediated noxious pulpal pain mechanisms by comparing expression patterns in pulpal nerves from healthy control molars to cold-sensitive painful molars with irreversible pulpitis. Samples were identically processed with the indirect immunofluorescence method and images obtained with confocal microscopy. The immunofluorescence intensity and area occupied by TRPM8 within N52/PGP9.5 identified nerve fibers were quantified. Results showed that relative to normal samples, TRPM8 nerve area expression was significantly less in the cold-sensitive painful samples (34.9% vs. 8%, p<0.03), but with no significant difference in immunofluorescence intensity between the two groups. These results suggest that TRPM8 is most likely not involved in coldmediated noxious pulpal pain mechanisms.

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“…6, 7). The importance of physiological temperature in brain functions has been studied in the hippocampus (Thompson et al, 1985;Anderson and Moser, 1995;de la Pena et al, 2005), although the molecular mechanisms have not been well clarified. Our findings indicate that TRPV4 activation at physiological core body temperature might partially underlie it.…”

Section: Trpv4 Contributes To Temperaturedependent Brain Functionmentioning

confidence: 99%

Effects of Body Temperature on Neural Activity in the Hippocampus: Regulation of Resting Membrane Potentials by Transient Receptor Potential Vanilloid 4

Shibasaki¹,

Suzuki²,

Mizuno³

et al. 2007

J. Neurosci.

266

195

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Physiological body temperature is an important determinant for neural functions, and it is well established that changes in temperature have dynamic influences on hippocampal neural activities. However, the detailed molecular mechanisms have never been clarified. Here, we show that hippocampal neurons express functional transient receptor potential vanilloid 4 (TRPV4), one of the thermosensitive TRP (transient receptor potential) channels, and that TRPV4 is constitutively active at physiological temperature. Activation of TRPV4 at 37°C depolarized the resting membrane potential in hippocampal neurons by allowing cation influx, which was observed in wild-type (WT) neurons, but not in TRPV4-deficient (TRPV4KO) cells, although dendritic morphology, synaptic marker clustering, and synaptic currents were indistinguishable between the two genotypes. Furthermore, current injection studies revealed that TRPV4KO neurons required larger depolarization to evoke firing, equivalent to WT neurons, indicating that TRPV4 is a key regulator for hippocampal neural excitabilities. We conclude that TRPV4 is activated by physiological temperature in hippocampal neurons and thereby controls their excitability.

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The contribution of TRPM8 channels to cold sensing in mammalian neurones

Cited by 69 publications

References 48 publications

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

TRPM8 Axonal Expression is Decreased in Painful Human Teeth with Irreversible Pulpitis and Cold Hyperalgesia

Effects of Body Temperature on Neural Activity in the Hippocampus: Regulation of Resting Membrane Potentials by Transient Receptor Potential Vanilloid 4

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