TRPM8 | Transient Receptor Potential Cation Channel M8
Family:
Transient receptor potential channels
Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN
Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations
TRPM8: Background information
TRPM8, also known as the cold and menthol receptor 1 (CMR1) is the primary transducer of cold somatosensation in humans. The TRPM8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices (S1–6). TRPM8 is an ion channel, upon activation it allows the entry of Na+ and Ca2+ ions to the cell that leads to depolarization and the generation of an action potential and it is activated by cold temperatures and cooling agents, such as menthol and icilin.
Gene:
TRPM8
Human Protein:
UniProt Q7Z2W7
Tissue:
Sensory neurons, dorsal root ganglia neurons, prostate, lung, bladder, prostatae tumors
Function/ Application:
Temperature transducer for ‘‘cold’’, proliferation, generation of an action potential
Pathology:
Cancer, thermoception, neuropathic pain, migrane, dentin sensitivity
Interaction:
TCAF1, PIP2, Gαq, Protein phosphatase 1, Ubiquitin specific peptidase 10
Modulator:
Cilin, eucalyptol, menthol, capsaicin, ethanol, linalool, geraniol, capsazepine , BCTC, cannabidiol
Assays:
Patch Clamp: whole cell, room temperature, State- and use-dependence
Particularities:
TRPM8 is a ligand-gated, intracellular pH- and thermo-sensitive ion channel
Recommended Reviews:International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003
Data and Applications
TRPM8 and Temperature Control
SyncroPatch 384 data and applications:
Cells were kindly provided by Charles River Chantest
At RT, the TRPM8 current was activated using increasing concentrations of Menthol (left). Measurement site, cells and solutions can be accurately temperature controlled – in the presence of temperatures 38°C, 25°C, 18°C and 12 °C the current size of temperature regulated TRPM8 changes accordingly (right). TRPM8 is activated at temperatures < 25°C.
TRPM8 / TRPV1 - Pharmacology
Port-a-Patch data and applications:
TRPV1 data were kindly supplied by Dr. David Cohen, Oregon Health and Service University, Portland, OR, USA.
TRP channels recorded in HEK293 cells. Menthol (dark blue) activated the TRPM8 channels (shown on the left) and could be inhibited by genistein (blue). TRPV1 channels expressed in HEK293 cells (right) were stimulated by application of capsaicin.
TRPM8 - Activated by Menthol
Port-a-Patch data and applications:
External application of 300 µM menthol activated the TRPM8 channels expressed in HEK293 cells.
Application Notes
TRPM8 / TRPV1 - "TRPV1 and TRPM8 recorded on Nanion's Port-a-Patch"
Port-a-Patch application note: 
(0.2 MB)
TRPM8 - Cold activation of TRPM8 using the External Perfusion System and the Port-a-Patch
Port-a-Patch application note: (3.63 MB)
TRPM8 - "TRPM8 activation by menthol and Eucalyptol performed on Nanion’s Patchliner"
Patchliner application note: (0.4 MB)
Cells were kindly provided by Charles River.
Publications
2019 - Purification of Functional Human TRP Channels Recombinantly Produced in Yeast
Orbit mini publication in Cells (2019)
Authors:
Zhang L., Wang K., Klaerke D.A., Calloe K., Lowrey L., Pedersen P.A., Gourdon P., Gotfryd K.
2018 - Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes
Port-a-Patch publication in Frontiers in Pharmacology (2018)
Authors:
Türker, E., Garreis, F., Khajavi, N., Reinach, P.S., Joshi, P., Brockmann, T., Lucius, A., Ljubojevic, N., Turan, E., Cooper, D., Schick, F., Reinholz, R., Pleyer, U., Köhrle, J., Mergler, S.
2018 - TRPM8 Activation via 3-Iodothyronamine Blunts VEGF-Induced Transactivation of TRPV1 in Human Uveal Melanoma Cells
Port-a-Patch publication in Frontiers in Pharmacology (2018)
Authors:
Walcher, L., Budde, C., Böhm, A., Reinach, P.S., Dhandapani, P., Ljubojevic, N., Schweiger, M.W., von der Waydbrink, H., Reimers, I., Köhrle, J., Mergler, S.
2018 - 3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines
Port-a-Patch publication in Frontiers in Endocrinology (2018)
Authors:
Bräunig J., Mergler S., Jyrch S., Hoefig C.S., Rosowski M., Mittag J., Biebermann H., Khajavi N.
2014 - Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells
Port-a-Patch publication in Cellular Signalling (2014)
Authors:
Mergler S., Derckx R., Reinach P.S., Garreis F., Böhm A., Schmelzer L., Skosyrski S., Ramesh N., Abdelmessih S., Polat O.K., Khajavi N., Riechardt A.I.
2013 - Functional significance of thermosensitive transient receptor potential melastatin channel 8 (TRPM8) expression in immortalized human corneal endothelial cells
Port-a-Patch publication in Experimental Eye Research (2013)
Authors:
Mergler S., Mertens C., Valtink M., Reinach P.S., Castelo Székely V., Slavi N., Abdelmessih S., Türker E., Fels G., Pleyer U.