cfpdБюллетень физиологии и патологии дыханияBulletin Physiology and Pathology of Respiration1998-5029Дальневосточный научный центр физиологии и патологии дыханияcfpd-442Research ArticleСтатьиТермочувствительные ионные каналы TRPM8 (обзор литературы)THERMOSENSITIVE ION CHANNELS TRPM8 (REVIEW)НаумовДенис ЕвгеньевичNaumovDenis E.denn1985@bk.ruДальневосточный научный центр физиологии и патологии дыхания Сибирского отделения РАМН, БлаговещенскFar Eastern Science centre physiology and pathology of respiration2011190220200428996Copyright © Наумов Д.Е., 20202020Наумов Д.Е.Naumov D.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cfpd.elpub.ru/jour/article/view/442

Способность к восприятию температурных стимулов обеспечивает основу для формирования адаптационных реакций, направленных на активное устранение возникшей угрозы или нарушений температурного гомеостаза. В последние десятилетия в качестве терморецепторов были идентифицированы некоторые представители семейства катионных каналов с транзиторным рецепторным потенциалом (TRP). Исследования последних лет указывают на их возможную вовлеченность в ряд физиологических процессов и патологических состояний. Более того, к настоящему времени было установлено, что термочувствительные TRP каналы способны опосредовать некоторые реакции со стороны респираторного тракта. В настоящем обзоре рассмотрены современные данные по генетике, молекулярной структуре и регуляции TRPM8-ионного канала, активируемого низкими температурами.

The ability to perceive temperature provides the basis for adaptive responses aimed at the active elimination of the threat or of the disturbance in temperature homeostasis. During last decades some members of transient receptor potential (TRP) cation channels family have been identified as thermoreceptors. Recent studies indicate their possible involvement in a number of physiological processes and pathological states. Moreover, it has been confirmed by now that thermosensitive TRP channels are capable to mediate certain respiratory responses. This review contains modern data on genetics, molecular structure and regulation of TRPM8-the ion channel activated by cold temperatures.

терморецепцияхолодтранзиторный рецепторный потенциалионные каналыTRPM8thermoreceptioncoldtransient receptor potentialion channelsTRPM8ReferencesСвязь однонуклеотидного полиморфизма rs11562975 гена термочувствительного ионного канала TRPM8 с чувствительностью человека к холоду и ментолу / Т.В.Козырева [и др.] // Физиол. человека. 2011. Т.37, №2. С.71-76.Связь однонуклеотидного полиморфизма rs11562975 гена термочувствительного ионного канала TRPM8 с чувствительностью человека к холоду и ментолу / Т.В.Козырева [и др.] // Физиол. человека. 2011. Т.37, №2. С.71-76.Ассоциация полиморфизма гена холодового рецептора TRPM8 с липидными показателями крови и антропометрическими параметрами у шорцев / Т.А.Потапова [и др.] // Бюл. эксп. биол. и мед. 2011. Т.151, №2. С.186-189.Ассоциация полиморфизма гена холодового рецептора TRPM8 с липидными показателями крови и антропометрическими параметрами у шорцев / Т.А.Потапова [и др.] // Бюл. эксп. биол. и мед. 2011. Т.151, №2. С.186-189.Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids / F.Abeele [et al.] // J. Biol. Chem. 2006. Vol.281, №52. P.40174-40182.Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids / F.Abeele [et al.] // J. Biol. Chem. 2006. Vol.281, №52. P.40174-40182.Andersson D.A., Chase H.W., Bevan S. TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH // J. Neurosci. 2004. Vol.24, №23. P.5364-5369.Andersson D.A., Chase H.W., Bevan S. TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH // J. Neurosci. 2004. Vol.24, №23. P.5364-5369.Andersson D.A., Nash M., Bevan S. Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids // J. Neurosci. 2007. Vol.27, №12. P.3347-3355.Andersson D.A., Nash M., Bevan S. Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids // J. Neurosci. 2007. Vol.27, №12. P.3347-3355.High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol / M.Bandell [et al.] // Nat. Neurosci. 2006. Vol.9, №4. P.493-500.High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol / M.Bandell [et al.] // Nat. Neurosci. 2006. Vol.9, №4. P.493-500.Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (flipr) assay / Behrendt H.J. [et al.] // Br. J. Pharmacol. 2004. Vol.141, №4. P.737-745.Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (flipr) assay / Behrendt H.J. [et al.] // Br. J. Pharmacol. 2004. Vol.141, №4. P.737-745.Brauchi S., Orio P., Latorre R. Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8 // Proc. Natl. Acad. Sci. USA. 2004. Vol.101, №43. P.15494-15499.Brauchi S., Orio P., Latorre R. Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8 // Proc. Natl. Acad. Sci. USA. 2004. Vol.101, №43. P.15494-15499.A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels / S.Brauchi [et al.] // J. Neurosci. 2006. Vol.26, №18. P.4835-4840.A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels / S.Brauchi [et al.] // J. Neurosci. 2006. Vol.26, №18. P.4835-4840.Genome-wide association study reveals three susceptibility loci for common migraine in the general population / D.I.Chasman [et al.] // Nature Genetics. 2011. Vol. 43. P.695-698.Genome-wide association study reveals three susceptibility loci for common migraine in the general population / D.I.Chasman [et al.] // Nature Genetics. 2011. Vol. 43. P.695-698.TRPM8 mediates cold and menthol allergies associated with mast cell activation / Y.Cho [et al.] // Cell Calcium. 2010. Vol.48, №4. P.202-208.TRPM8 mediates cold and menthol allergies associated with mast cell activation / Y.Cho [et al.] // Cell Calcium. 2010. Vol.48, №4. P.202-208.Chuang H.H., Neuhausser W.M., Julius D. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel // Neuron. 2004. Vol.43. P.859-869.Chuang H.H., Neuhausser W.M., Julius D. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel // Neuron. 2004. Vol.43. P.859-869.Clapham D.E. TRP channels as cellular sensors // Nature. 2003. Vol.426, №6966. P.517-524.Clapham D.E. TRP channels as cellular sensors // Nature. 2003. Vol.426, №6966. P.517-524.Damann N., Voets T., Nilius B. TRPs in our senses // Curr. Biol. 2008. Vol.18, №18. P.R880-889.Damann N., Voets T., Nilius B. TRPs in our senses // Curr. Biol. 2008. Vol.18, №18. P.R880-889.Cold weather exercise and airway cytokine expression / M.S.Davis [et al.] // J. Appl. Physiol. 2005. Vol.98. P.2132-2136.Cold weather exercise and airway cytokine expression / M.S.Davis [et al.] // J. Appl. Physiol. 2005. Vol.98. P.2132-2136.Dragoni I., Guida E., McIntyre P. The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif // J. Biol. Chem. 2006. Vol.281, №49. P.37353-37360.Dragoni I., Guida E., McIntyre P. The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif // J. Biol. Chem. 2006. Vol.281, №49. P.37353-37360.Earley S. Vanilloid and melastatin transient receptor potential channels in vascular smooth muscle // Microcirculation. 2010. Vol.17, №4. P.237-249.Earley S. Vanilloid and melastatin transient receptor potential channels in vascular smooth muscle // Microcirculation. 2010. Vol.17, №4. P.237-249.Trafficking and assembly of the cold-sensitive TRPM8 channel / I.Erler [et al.] // J. Biol. Chem. 2006. Vol.281, №50. P.38396-38404.Trafficking and assembly of the cold-sensitive TRPM8 channel / I.Erler [et al.] // J. Biol. Chem. 2006. Vol.281, №50. P.38396-38404.Fujiwara Y., Minor D.L.Jr. X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil // J. Mol. Biol. 2008. Vol.383, №4. P.854-870.Fujiwara Y., Minor D.L.Jr. X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil // J. Mol. Biol. 2008. Vol.383, №4. P.854-870.Identification of a tetramerization domain in the C terminus of the vanilloid receptor / N.García-Sanz [et al.] // J. Neurosci. 2004. Vol.24, №23. P.5307-5314.Identification of a tetramerization domain in the C terminus of the vanilloid receptor / N.García-Sanz [et al.] // J. Neurosci. 2004. Vol.24, №23. P.5307-5314.The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity / C.Gentry [et al.] // Mol. Pain. 2010. Vol.6. P.4.The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity / C.Gentry [et al.] // Mol. Pain. 2010. Vol.6. P.4.Homo- and heterotetrameric architecture of the epithelial Ca21 channels TRPV5 and TRPV6 / J.G.Hoenderop [et al.] // EMBO J. 2003. Vol.22. P.776-785.Homo- and heterotetrameric architecture of the epithelial Ca21 channels TRPV5 and TRPV6 / J.G.Hoenderop [et al.] // EMBO J. 2003. Vol.22. P.776-785.Huang C.L. The transient receptor potential superfamily of ion channels // J. Am. Soc. Nephrol. 2004. Vol.15. P.1690-1699.Huang C.L. The transient receptor potential superfamily of ion channels // J. Am. Soc. Nephrol. 2004. Vol.15. P.1690-1699.Hui K., Guo Y., Feng Z.P. Biophysical properties of menthol-activated cold receptor TRPM8 channels // Biochem. Biophys. Res. Commun. 2005. Vol.333, №2. P.374-382.Hui K., Guo Y., Feng Z.P. Biophysical properties of menthol-activated cold receptor TRPM8 channels // Biochem. Biophys. Res. Commun. 2005. Vol.333, №2. P.374-382.Koskela H.O. Cold air-provoked respiratory symptoms: the mechanisms and management // Int. J. Circumpolar Health. 2007. Vol.66. P.91-100.Koskela H.O. Cold air-provoked respiratory symptoms: the mechanisms and management // Int. J. Circumpolar Health. 2007. Vol.66. P.91-100.Kühn F.J., Knop G., Lückhoff A. The transmembrane segment S6 determines cation versus anion selectivity of TRPM2 and TRPM8 // J. Biol. Chem. 2007. Vol.282, №38. P.27598-27609.Kühn F.J., Knop G., Lückhoff A. The transmembrane segment S6 determines cation versus anion selectivity of TRPM2 and TRPM8 // J. Biol. Chem. 2007. Vol.282, №38. P.27598-27609.Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects / K.Larsson [et al.] // Eur. Respir. J. 1998. Vol.12. P.825-830.Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects / K.Larsson [et al.] // Eur. Respir. J. 1998. Vol.12. P.825-830.Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism / M.Li [et al.] // J. Allergy Clin. Immunol. 2011. Vol.128, №3. P.626-634.Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism / M.Li [et al.] // J. Allergy Clin. Immunol. 2011. Vol.128, №3. P.626-634.Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators / R.M.Linte [et al.] // Exp. Brain Res. 2007. Vol.178, №1. P.89-98.Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators / R.M.Linte [et al.] // Exp. Brain Res. 2007. Vol.178, №1. P.89-98.Liu B., Qin F. Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate // J. Neurosci. 2005. Vol.25, №7. P.1674-1681.Liu B., Qin F. Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate // J. Neurosci. 2005. Vol.25, №7. P.1674-1681.Liu D., Liman E.R. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5 // Proc. Natl. Acad. Sci. USA. 2003. Vol.100, №25. P.15160-15165.Liu D., Liman E.R. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5 // Proc. Natl. Acad. Sci. USA. 2003. Vol.100, №25. P.15160-15165.Molecular identification and functional characterization of a temperature-sensitive transient receptor potential channel (TRPM8) from canine / Y.Liu [et al.] // Eur. J. Pharmacol. 2006. Vol.530, №1-2. P.23-32.Molecular identification and functional characterization of a temperature-sensitive transient receptor potential channel (TRPM8) from canine / Y.Liu [et al.] // Eur. J. Pharmacol. 2006. Vol.530, №1-2. P.23-32.Lundbaek J.A., Andersen O.S. Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers // J. Gen. Physiol. 1994. Vol.104, №4. P.645-673.Lundbaek J.A., Andersen O.S. Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers // J. Gen. Physiol. 1994. Vol.104, №4. P.645-673.Thermal mapping of the airways in humans / E.R.Jr.McFadden [et al.] // J. Appl. Physiol. 1985. Vol.58, №2. P.564-570.Thermal mapping of the airways in humans / E.R.Jr.McFadden [et al.] // J. Appl. Physiol. 1985. Vol.58, №2. P.564-570.McKemy D.D., Neuhausser W.M., Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation // Nature. 2002. Vol.416, №6876. P.52-58.McKemy D.D., Neuhausser W.M., Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation // Nature. 2002. Vol.416, №6876. P.52-58.Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticaria / N.Medic [et al.] // Cell. Calcium. 2011. Vol.50, №5. P.473-480.Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticaria / N.Medic [et al.] // Cell. Calcium. 2011. Vol.50, №5. P.473-480.Minke B., Cook B. TRP channel proteins and signal transduction // Physiol. Rev. 2002. Vol.82. P.429-472.Minke B., Cook B. TRP channel proteins and signal transduction // Physiol. Rev. 2002. Vol.82. P.429-472.Montell C. A mint of mutations in TRPM8 leads to cool results // Nat. Neurosci. 2006. Vol.9. P.466-468.Montell C. A mint of mutations in TRPM8 leads to cool results // Nat. Neurosci. 2006. Vol.9. P.466-468.Murakami M., Kudo I. Phospholipase A2 // J. Biochem. 2002. Vol.131, №3. P.285-292.Murakami M., Kudo I. Phospholipase A2 // J. Biochem. 2002. Vol.131, №3. P.285-292.Myers B.R., Sigal Y.M., Julius D. Evolution of thermal response properties in a cold-activated TRP channel // PLoS One. 2009. Vol.4, №5. P.5741.Myers B.R., Sigal Y.M., Julius D. Evolution of thermal response properties in a cold-activated TRP channel // PLoS One. 2009. Vol.4, №5. P.5741.Permeation and selectivity of TRP channels / G.Owsianik [et al.] // Annu. Rev. Physiol. 2006. Vol.68. P.685-717.Permeation and selectivity of TRP channels / G.Owsianik [et al.] // Annu. Rev. Physiol. 2006. Vol.68. P.685-717.Pak W.L., Grossfield J., Arnold K.S. Mutants of the visual pathway of Drosophila melanogaster // Nature. 1970. Vol.227, №5257. P.518-520.Pak W.L., Grossfield J., Arnold K.S. Mutants of the visual pathway of Drosophila melanogaster // Nature. 1970. Vol.227, №5257. P.518-520.ThermoTRP channels and beyond: mechanisms of temperature sensation / A.Patapoutian [et al.] // Nat. Rev. Neurosci. 2003. Vol.4, №7. P.529-539.ThermoTRP channels and beyond: mechanisms of temperature sensation / A.Patapoutian [et al.] // Nat. Rev. Neurosci. 2003. Vol.4, №7. P.529-539.A TRP channel that senses cold stimuli and menthol / A.M.Peier [et al.] // Cell. 2002. Vol.108, №5. P.705-715.A TRP channel that senses cold stimuli and menthol / A.M.Peier [et al.] // Cell. 2002. Vol.108, №5. P.705-715.Phelps C.B., Gaudet R. The role of the N terminus and transmembrane domain of TRPM8 in channel localization and tetramerization // J. Biol. Chem. 2007. Vol.282, №50. P.36474-36480.Phelps C.B., Gaudet R. The role of the N terminus and transmembrane domain of TRPM8 in channel localization and tetramerization // J. Biol. Chem. 2007. Vol.282, №50. P.36474-36480.Pisarri T.E., Giesbrecht G.G. Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs // J. Appl. Physiol. 1997. Vol.82, №5. P.1566-1572.Pisarri T.E., Giesbrecht G.G. Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs // J. Appl. Physiol. 1997. Vol.82, №5. P.1566-1572.PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain / T.Rohács [et al.] // Nat. Neurosci. 2005. Vol.8, №5. P.626-634.PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain / T.Rohács [et al.] // Nat. Neurosci. 2005. Vol.8, №5. P.626-634.Human Lung Epithelial Cells Express a Functional Cold-Sensing TRPM8 Variant / A.S.Sabnis [et al.] // Am. J. Respir. Cell. Mol. Biol. 2008. Vol.9. P.466-474.Human Lung Epithelial Cells Express a Functional Cold-Sensing TRPM8 Variant / A.S.Sabnis [et al.] // Am. J. Respir. Cell. Mol. Biol. 2008. Vol.9. P.466-474.Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures / A.S.Sabnis [et al.] // Am. J Physiol. Lung Cell. Mol. Physiol. 2008. Vol.295, №1. P.194-200.Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures / A.S.Sabnis [et al.] // Am. J Physiol. Lung Cell. Mol. Physiol. 2008. Vol.295, №1. P.194-200.A novel mechanism for the store-operated calcium influx pathway / T.Smani [et al.] // Nat. Cell. Biol. 2004. Vol.6, №2. P.113-120.A novel mechanism for the store-operated calcium influx pathway / T.Smani [et al.] // Nat. Cell. Biol. 2004. Vol.6, №2. P.113-120.AFM imaging reveals the tetrameric structure of the TRPM8 channel / A.P.Stewart [et al.] // Biochem. Biophys. Res. Commun. 2010. Vol.394, №2. P.383-386.AFM imaging reveals the tetrameric structure of the TRPM8 channel / A.P.Stewart [et al.] // Biochem. Biophys. Res. Commun. 2010. Vol.394, №2. P.383-386.Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells / S.Thebault [et al.] // J. Biol. Chem. 2005. Vol.280, №47. P.39423-39435.Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells / S.Thebault [et al.] // J. Biol. Chem. 2005. Vol.280, №47. P.39423-39435.Asymmetrical membranes and surface tension / M.Traïkia [et al.] // Biophys. J. 2002. Vol.83, №3. P.1443-1454.Asymmetrical membranes and surface tension / M.Traïkia [et al.] // Biophys. J. 2002. Vol.83, №3. P.1443-1454.Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins / L.Tsavaler [et al.] // Cancer Res. 2001. Vol.61, №9. P.3760-3769.Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins / L.Tsavaler [et al.] // Cancer Res. 2001. Vol.61, №9. P.3760-3769.Tsuruda P.R., Julius D., Minor D.L.Jr. Coiled coils direct assembly of a cold-activated TRP channel // Neuron. 2006. Vol.51, №2. P.201-212.Tsuruda P.R., Julius D., Minor D.L.Jr. Coiled coils direct assembly of a cold-activated TRP channel // Neuron. 2006. Vol.51, №2. P.201-212.Functional role of C-terminal cytoplasmic tail of rat vanilloid receptor 1 / V.Vlachová [et al.] // J. Neurosci. 2003. Vol.23, №4. P.1340-1350.Functional role of C-terminal cytoplasmic tail of rat vanilloid receptor 1 / V.Vlachová [et al.] // J. Neurosci. 2003. Vol.23, №4. P.1340-1350.The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels / T.Voets [et al.] // Nature. 2004. Vol.430, №7001. P.748-754.The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels / T.Voets [et al.] // Nature. 2004. Vol.430, №7001. P.748-754.TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli / T.Voets [et al.] // Nat. Chem. Biol. 2007. Vol.3, №3. P.174-182.TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli / T.Voets [et al.] // Nat. Chem. Biol. 2007. Vol.3, №3. P.174-182.Vriens J., Appendino G., Nilius B. Pharmacology of vanilloid transient receptor potential cation channels // Mol. Pharmacol. 2009. Vol.75, №6. P.1262-1279.Vriens J., Appendino G., Nilius B. Pharmacology of vanilloid transient receptor potential cation channels // Mol. Pharmacol. 2009. Vol.75, №6. P.1262-1279.TRPM8 mechanism of autonomic nerve response to cold in respiratory airway / H.Xing [et al.] // Mol. Pain. 2008. Vol.4. P.22.TRPM8 mechanism of autonomic nerve response to cold in respiratory airway / H.Xing [et al.] // Mol. Pain. 2008. Vol.4. P.22.

The authors declare that there are no conflicts of interest present.