TRPM3

TRPM3 is the acronym for "Transient receptor potential cation channel, subfamily M, member 3". The melastatin-related Transient Receptor Potential (TRP) channel is a non-selective cation channel expressed in nociceptive neurons and activated by heat, among other stimuli. The TRPM3 gene is located on chromosome 9q21.12-q21.13. The encoded cation channel belongs to the superfamily of ion channels with transient receptor potential (TRP).

TRPM3 belongs to the family of melastatin -related transient receptor (TRPM) channels. TRPMs are Ca(2+)-permeable cation channels that are predominantly localized to the plasma membrane. The structural machinery of TRPM channels includes intracellular N- and C-termini, 6 transmembrane segments, and a pore region between segments 5 and 6. The N-terminal domain has a conserved region, and the C-terminal domain contains a TRP motif, a coiled-coil region, and, in some TRPM channels, an enzymatic domain. TRPM3, unlike other TRPM channels, is activated by sphingosine (Farooqi et al. 2011). Its activation triggers a signal transduction cascade of mitogen-activated kinases and stimulus response transcription factors.

Studies in sensory neurons showed that TRPM3 channels contribute to heat responses, but also that they function as heat sensors for noxious heat-noxious heat sensor- (Vriens J et al. 2011 and 2018).

Other activators of TRPM3 channels besides heat include the neurosteroid pregnenolone sulfate, calmodulin, and phosphoinositides.

Highly efficient TRPM3 blockers with pronounced specificity for the receptor are the nonsteroidal anti-inflammatory drug diclofenac, the tetracyclic antidepressant maprotiline and the anticonvulsant primidone (Krügel U et al. 2017).

The mammalian TRPM3 gene harbors a noncoding microRNA gene specified miR-204 that serves as both a tumor suppressor and a negative regulator of posttranscriptional gene expression during vertebrate eye development. Ocular co-expression of TRPM3 and miR-204 is upregulated by a transcription factor (PAX6). Mutations in all three corresponding genes underlie hereditary forms of eye disease in humans, including early-onset cataract, retinal dystrophy, and coloboma (Shiels A 2020).

1. Farooqi A A et al. (2011) TRPM channels: same ballpark, different players, and different rules in immunogenetics. Immunogenetics 63: 773-787
2. Krügel U et al (2017) Primidone inhibits TRPM3 and attenuates thermal nociception in vivo. Pain158: 856-867.
3. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
4. Shiels A (2020) TRPM3_miR-204: a complex locus for eye development and disease. Hum Genomics 14:7.
5. Vriens J et al (2011) TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron 70: 482-494
6. Vriens J et al (2018) Sensing the heat with TRPM3. Pflugers Arch 470:799-807.