TRPM3

TRPM3 is a member of the transient receptor potential (TRP) ion channel family. The gene encodes a non-selective cation channel that is permeable to calcium (Ca2+) and other cations and forms functional channels as tetramers in the plasma membrane. TRPM3 channels can be activated by chemical ligands, heat, and cellular signals, leading to depolarization and intracellular calcium increase.

Expression and function are most prominent in sensory neurons, including dorsal root and trigeminal ganglion neurons, where TRPM3 contributes to thermal nociception and the perception of heat. The channel is also found in pancreatic beta cells and various other tissues, where it participates in calcium signaling that can influence cellular processes such as hormone secretion. In addition to heat sensitivity, pregnenolone sulfate (PregS) is a potent endogenous activator of TRPM3, linking neurosteroid signaling to calcium entry through these channels.

Regulation of TRPM3 involves lipid and intracellular signals; phosphoinositides and other modulators can influence channel activity. Pharmacological tools include activators such as PregS and heat, and blockers that are used to study TRPM3 function in research settings, including certain divalent cations and classical TRP antagonists. Because TRPM3 links chemical, thermal, and steroid signaling to calcium influx, it is a subject of interest in studies of nociception, arrhythmias in smooth muscle, and metabolic signaling in pancreatic cells.

Clinical relevance remains an area of active investigation. TRPM3 is considered a potential target for modulating pain and other calcium-dependent physiological processes, with ongoing research into selective modulators and their therapeutic prospects.