Transient receptor potential cation channel subfamily M member 3 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''TRPM3''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

The product of this gene belongs to the family of transient receptor potential (TRP) channels. TRP channels are Ca²⁺ permeable non-selective cation channels that play roles in a wide variety of physiological processes, including calcium signaling, heat and cold sensation, calcium and magnesium homeostasis. TRPMs mediates sodium and calcium entry, which induces

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

and a cytoplasmic Ca²⁺ signal. Alternatively spliced transcript variants encoding different isoforms have been -identified. TRPM3 was shown to be activated by the neurosteroid pregnenolone sulfate as well as the synthetic compound CIM0216.

Peripheral heat sensation

TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia, and they are activated by high temperatures. Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal

hyperalgesia Hyperalgesia ( or ; ''hyper'' from Greek ὑπέρ (''huper'') 'over' + ''-algesia'' from Greek ἄλγος (algos) 'pain') is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and ...

. Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia, as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain.

Receptor mediated inhibition

TRPM3 is robustly inhibited by the activation of cell surface receptors that couple to inhibitory heterotrimeric G-proteins (Gi) via direct binding of the Gβγ subunit of the G-protein to the channel. Gβγ was shown to bind to a short α-helical segment of the channel. Receptors that inhibit TRPM3 include opioid receptors and GABA_B receptors.

TRPM3 in the brain

Mutations in TRPM3 in humans, were recently shown to cause a intellectual disability and

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

. The disease associated mutations were shown to increase the sensitivity of the channel to agonists, and heat.

TRPM3 ligands, activators and modulators

Activators

*Heat * Pregnenolone Sulfate * CIM-0216

Channel Blockers

# Mefenamic acid #

Citrus fruit ''Citrus'' is a genus of flowering plant, flowering trees and shrubs in the family Rutaceae. Plants in the genus produce citrus fruits, including important crops such as Orange (fruit), oranges, Mandarin orange, mandarins, lemons, grapefruits, ...

flavonoids, e.g. naringenin, isosakuranetin and hesperetin, as well as ononetin (a deoxybenzoin). # Primidone, a clinically used

antiepileptic Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatmen ...

medication also directly inhibits TRPM3.

Activity Modulator

* pH

References

External links

* {{Transient receptor potential channel modulators Ion channels