Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones

Reid, Gordon; Flonta, Maria-Luiza

doi:10.1016/s0304-3940(02)00181-7

Cited by 65 publications

(50 citation statements)

References 16 publications

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“…TRPM8, like TRPV1, is also expressed in sensory neurons in the peripheral nervous system, especially in dorsal root, trigeminal, and nodose ganglia (McKemy et al, 2002;Peier et al, 2002;Reid and Flonta, 2002;Nealen et al, 2003;Thut et al, 2003;Zhang et al, 2004). This, combined with clinical reports that document the beneficial effects of menthol treatment in patients suffering from postherpetic neuralgia and irritable bowel syndrome (Pittler and Ernst, 1998;Davies et al, 2002), suggests that TRPM8 may also be an exciting new target for the development of novel analgesics and agents to treat a range of other conditions (Caterina et al, 1997;McKemy et al, 2002;Peier et al, 2002).…”

Section: (2h)-carboxamide (Bctc) (2r)-4-(3-chloro-2-pyridinyl)-2-metmentioning

confidence: 99%

“…Antagonist solutions were prepared as 10 mM stock solutions in dimethyl sulfoxide before dilution in extracellular solution. To minimize problems arising from the poor solubility of menthol, it was prepared as a 100 mM stock solution in ethanol before dilution in extracellular solution (final ethanol concentration ϭ 0.1%) (Reid and Flonta, 2002). For studies examining the effect of acid on TRPM8, the pH of the extracellular solution was adjusted to 6.3 or 5.3 by the addition of HCl.…”

Section: Downloaded Frommentioning

confidence: 99%

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Conservation of Functional and Pharmacological Properties in the Distantly Related Temperature Sensors TRPV1 and TRPM8

Weil

Moore²,

Waite³

et al. 2005

Mol Pharmacol

146

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Members of the transient receptor potential (TRP) superfamily of ion channels have now been defined as molecular transducers capable of reproducing the spectrum of temperature sensation exhibited by mammals. Because of their pivotal role in sensory transduction, many of these channels represent good targets for drug discovery. With a view to gaining further insight into the functional and pharmacological properties of these channels, we have used the whole-cell patch-clamp technique to study the human cold-sensitive menthol receptor transient receptor potential melastatin 8 (TRPM8) and compared its behavior with that of its distant relative, the heat-sensitive capsaicin-gated transient receptor potential vanilloid 1 (TRPV1). It is remarkable to find that TRPM8, in addition to its behavior as an outwardly rectifying, nonselective cation channel, shares many functional and pharmacological properties with TRPV1. TRPM8 exhibits prominent time-and voltage-dependent behavior, a property that may underlie the conserved rectification or gating mechanisms exhibited by these channels. We also show that TRPM8 is modulated by ethanol but unlike TRPV1 is insensitive to extracellular acidification. There is also significant overlap in the antagonist pharmacology of these channels with many TRPV1 antagonists such as capsazepine, -{2-[ethyl(3-methylphenyl)amino]ethyl}-urea (SB-452533) exhibiting similar activity at TRPM8. Overall, the degree of pharmacological overlap between TRPV1 and TRPM8 has implications for the interpretation of studies conducted with these ligands to date and highlights a clear challenge for the design of selective TRP channel antagonists. Our finding that N-(3-methoxyphenyl)-4-chlorocinnamide (SB-366791), at least, represents an apparently selective antagonist for TRPV1 suggests that this goal is attainable.

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Section: (2h)-carboxamide (Bctc) (2r)-4-(3-chloro-2-pyridinyl)-2-metmentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Conservation of Functional and Pharmacological Properties in the Distantly Related Temperature Sensors TRPV1 and TRPM8

Weil

Moore²,

Waite³

et al. 2005

Mol Pharmacol

146

View full text Add to dashboard Cite

show abstract

“…Cold and menthol appear to activate the channel via a membrane-delimited mechanism; however, pronounced differences are observed in excised patches and in intact neurons (Reid and Flonta, 2002;Voets et al, 2004). In particular, channels in excised patches show a strikingly low open probability, suggesting that the function of the receptor depends on the cellular environment.…”

Section: Introductionmentioning

confidence: 96%

Functional Control of Cold- and Menthol-Sensitive TRPM8 Ion Channels by Phosphatidylinositol 4,5-Bisphosphate

Liu¹,

Feng²

2005

J. Neurosci.

289

290

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Cold is detected by a small subpopulation of peripheral thermoreceptors. TRPM8, a cloned menthol-and cold-sensitive ion channel, has been suggested to mediate cold transduction in the innocuous range. The channel shows a robust response in whole-cell recordings but exhibits markedly reduced activity in excised membrane patches. Here we report that phosphatidylinositol 4,5-bisphosphate (PIP 2 ) is an essential regulator of the channel function. The rundown of the channel is prevented by lipid phosphatase inhibitors. Application of exogenous PIP 2 both activates the channel directly and restores rundown activity. Whole-cell experiments involving intracellular dialysis with polyvalent cations, inhibition of PIP 2 synthesis kinases, and receptor-mediated hydrolysis of PIP 2 show that PIP 2 also modulates the channel activity in the intact cells. The crucial role of PIP 2 on the function of TRPM8 suggests that the membrane PIP 2 level may be an important regulator of cold transduction in vivo. The opposite effects of PIP 2 on the vanilloid receptor TRPV1 and TRPM8 also implies that the membrane lipid may have dual actions as a bimodal switch to selectively control the heat-and cold-induced responses in nociceptors expressing both channels.

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“…Thus, TRPM8 can sense temperature changes in the range of both innocuous cold (15-28°C) and noxious cold (Ͻ15°C). TRPM8 can also be activated by menthol, an ingredient of peppermint that produces a cooling sensation (McKemy et al, 2002;Peier et al, 2002;Reid and Flonta, 2002). TRPM8-expressing neurons are ϳ10 -15% of the total trigeminal ganglion neuron population and 5-10% of the dorsal root ganglion (DRG) neuron population (McKemy et al, 2002;Peier et al, 2002;Abe et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Xiao¹,

Chen²,

Ling³

et al. 2007

J. Neurosci.

206

177

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The cold-and menthol-sensitive receptor TRPM8 (transient receptor potential melastatin 8) has been suggested to play a role in cold allodynia, an intractable pain seen clinically. We studied how TRPM8 is involved in cold allodynia using rats with chronic constrictive nerve injury (CCI), a neuropathic pain model manifesting cold allodynia in hindlimbs. We found that cold allodynic response in the CCI animals was significantly attenuated by capsazepine, a blocker for both TRPM8 and TRPV1 (transient receptor potential vanilloid 1) receptors, but not by the selective TRPV1 antagonist I-RTX (5-iodoresiniferatoxin). In L5 dorsal root ganglion (DRG) sections of the CCI rats, immunostaining showed an increase in the percentage of TRPM8-immunoreactive neurons when compared with the sham group. Using the Ca 2ϩ -imaging technique and neurons acutely dissociated from the L5 DRGs, we found that CCI resulted in a significant increase in the percentage of menthol-and cold-sensitive neurons and also a substantial enhancement in the responsiveness of these neurons to both menthol and innocuous cold. These changes occurred in capsaicin-sensitive neurons, a subpopulation of nociceptive-like neurons. Using patch-clamp recordings, we found that membrane currents evoked by both menthol and innocuous cold were significantly enhanced in the CCI group compared with the sham group. By retrograde labeling afferent neurons that target hindlimb skin, we showed that the skin neurons expressed TRPM8 receptors, that the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neurons increased, and that the menthol-and cold-evoked responses were significantly enhanced in capsaicin-sensitive neurons after CCI. Together, the gain of TRPM8-mediated cold sensitivity on nociceptive afferent neurons provides a mechanism of cold allodynia.

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Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones

Cited by 65 publications

References 16 publications

Conservation of Functional and Pharmacological Properties in the Distantly Related Temperature Sensors TRPV1 and TRPM8

Conservation of Functional and Pharmacological Properties in the Distantly Related Temperature Sensors TRPV1 and TRPM8

Functional Control of Cold- and Menthol-Sensitive TRPM8 Ion Channels by Phosphatidylinositol 4,5-Bisphosphate

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

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