TRPM8 Membrane Protein Introduction

Introduction of TRPM8

Transient receptor potential cation channel subfamily M member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is encoded by the TRPM8 gene. Similar to other members of the TRPM family, TRPM8 also contains a large N terminal hydrophilic domain with eight potential N-linked glycosylation sites, a putative C-terminal coiled coil that is important for channel assembly, trafficking, and function and 6 transmembrane domains. The TRPM8 channel is the most important ion channel acting as a molecular transducer of cold somatosensation in humans.

Basic Information of TRPM8
Protein Name Transient receptor potential cation channel subfamily M member 8
Gene Name TRPM8
Aliases LTRPC6, TRPP8, CMR1
Organism Homo sapiens (Human)
UniProt ID Q7Z2W7
Transmembrane Times 6
Length (aa) 1104

Function of TRPM8 Membrane Protein

TRPM8 is a non-selective cation channel allowing the influx of Ca²⁺ and Na⁺ ions to the cell that leads to the depolarization of the plasma membrane and the generation of an action potential. In addition, TRPM8 is characterized as a detector of cold and it is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. TRPM8 shows the property of a polymodal sensor that can integrate multiple chemical and physical stimuli into cellular signaling. Except for cold temperatures, TRPM8 can be activated by a number of chemical agonists that are known to produce cool sensations such as menthol and eucalyptol. In addition to cold and menthol, TRPM8 is sensitive to voltage and phosphatidylinositol-4,5-bisphosphate (PIP2). The contribution of TRPM8 to both analgesia and nociception has been demonstrated, suggesting TRPM8 is a therapeutic target for treatment of cold-related pain, chronic pain, and migraine. It is reported that TRPM8 is indispensable for the survival and proliferation of prostate cancer cells, suggesting that targeting TRPM8 ion channels may be a potential approach to treat prostate cancer.

Schematic representation of TRPM8 structure in the plasma membrane. Fig.1 Schematic representation of TRPM8 structure in the plasma membrane. (Yee, 2015)

Application of TRPM8 Membrane Protein in Literature

  1. Bereiter D.A., et al. TRPV1 and TRPM8 Channels and Nocifensive Behavior in a Rat Model for Dry Eye. Invest Ophthalmol Vis Sci. 2018, 59(8):3739-3746. PubMed ID: 30046815

    This article suggests that TRPV1 may have a critical role in regulating enhanced nocifensive behavior in dry eye disease, while TRPM8 may play a relatively lesser role.

  2. Gao T., et al. Activation of TRPM8 cold receptor triggers allodynia-like behavior in spinally injured rats. Scand J Pain. 2013, 4(1):33-37. PubMed ID: 29913874

    This article shows that activation of the TRPM8 ion channel by icilin or menthol triggers allodynia in spinally injured rats and increases, rather than decreases, mechanical allodynia.

  3. Pertusa M., et al. Critical role of the pore domain in the cold response of TRPM8 channels identified by ortholog functional comparison. J Biol Chem. 2018, 293(32):12454-12471. PubMed ID: 29880642

    This article reveals that these structural domains are deeply associated with functional modulation and cold sensitivity of TRPM8, and suggests that the pore domain may be the crucial molecular determinant in temperature responses of this thermo-transient receptor potential channel.

  4. Key F.M., et al. Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. PLoS Genet. 2018, 14(5):e1007298. PubMed ID: 29723195

    This article forms a hypothesis that local adaptation on previously neutral standing variation may be associated with the genetic differences that exist in the prevalence of migraine among human populations today.

  5. Chan H., et al. TRPM8 and RAAS-mediated hypertension is critical for cold-induced immunosuppression in mice. Oncotarget. 2018, 9(16):12781-12795. PubMed ID: 29560109

    This article confirms that the natively raised level of plasma immunoglobulin is associated with immunosuppression under the condition of cold exposure, and antihypertensive drugs can be used to mediate immunosuppression induced by cold exposure.

TRPM8 Preparation Options

In order to provide a high-quality membrane protein preparation service, we have developed the versatile Magic™ membrane protein production platform. Our experienced scientists will do their best to help you find a perfect match in your required formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TRPM8 antibody development services.

The membrane protein service team in Creative Biolabs has several years of experience in membrane protein preparation using our efficient and validated strategies. With our integrated multiple cutting-edge technologies, we are proud to offer the most comprehensive membrane protein preparation services in required formats. If you are interested in the service we can provide, please feel free to contact us for more information.


  1. Yee N S. (2015). Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion. Cancers (Basel). 7(4):2134-46.

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