TRPM8

Transient receptor potential cation channel subfamily M member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans.

Structure

The TRPM8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices (S1-S6). The first four, S1-S4, act as the voltage sensor and allow binding of menthol, icilin and similar channel agonists. S5 and S6 and a connecting loop, also part of the structure, make up the pore, a non-selective cation channel which consists of a highly conserved hydrophobic region, A range of diverse components are required for the high level of specificity in responding to result in ion flow to cold and menthol stimuli.

Function

TRPM8 is an ion channel, upon activation it allows the entry of Na+ (sodium) and Ca2+ (calcium) ions to the cell that leads to depolarization and the generation of an action potential. The signal is conducted from primary afferents (type C- and A-delta) eventually leading to the sensation of cold and cold pain.

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