Pro-nociceptive and pro-inflammatory TRPM3 (transient receptor potential melastatin 3) channels, expressed in somatosensory neurons, are inhibited by activation of Gαi-coupled receptors, such as µ-opioid receptors, in vitro and in vivo.
Two mutations in TRPM3 resulting in developmental and epileptic encephalopathies result in a gain-of-channel function, which may lie at the basis of epileptic activity and neurodevelopmental symptoms in the patients.
Disease-associated mutants of the TRPM3 ion channel are overactive, and they are inhibited by the antiepileptic medication primidone, offering a potential therapeutic intervention to treat this channelopathy.
Mice deficient in the TRPM6 channel suffer from impaired prenatal development, shortened lifespan, growth deficit and disturbed energy balance due to a defect in epithelial Mg2+ uptake, thus highlighting a pivotal role of TRPM6 in organismal Mg2+ homeostasis.
The 3Å structure and correlated functional analysis of the TRPM2 cation channel from Nematostella vectensis shed light on the molecular mechanisms of TRPM2 regulation by intra- and extracellular Ca2+, and of inactivation of human TRPM2.