Transient receptor potential cation channel subfamily M member 3 (TRPM3) (TRPM3)

Transient receptor potential melastatin 3 (TRPM3) is a calcium-permeable, non-selective cation channel primarily expressed in small-diameter primary sensory neurons (nociceptors) of the dorsal root and trigeminal ganglia. It serves as a critical molecular sensor for noxious heat and is chemically activated by the neurosteroid pregnenolone sulfate. TRPM3 activation leads to cation influx, neuronal depolarization, and the release of calcitonin gene-related peptide (CGRP), which contributes to neurogenic inflammation and pain hypersensitivity. Recent research has identified TRPM3 as a key component of a novel pain-sensing pathway that is physiologically inhibited by G-protein-coupled receptors, such as the mu-opioid receptor, via the direct action of Gβγ subunits. This discovery positions TRPM3 as a promising therapeutic target for non-addictive analgesics, with several small-molecule inhibitors currently in development for inflammatory and neuropathic pain conditions.

Other names

Melastatin-2LTRPC3MLSN2Long transient receptor potential channel 3Transient receptor potential cation channel subfamily M member 3

TRPM3 is a non-selective cation channel that mediates the influx of calcium and sodium ions in response to noxious heat and chemical agonists like pregnenolone sulfate. Inhibition of this channel reduces the excitability of nociceptive neurons and the subsequent release of pro-inflammatory neuropeptides such as CGRP, thereby providing analgesic and anti-inflammatory effects.