TRPM5

TRPM5 (transient receptor potential cation channel subfamily M member 5) is a member of the TRP channel family that forms a calcium-activated, nonselective cation channel. It is predominantly permeable to monovalent cations such as sodium and potassium, with limited permeability to calcium. Activation occurs in response to rises in intracellular calcium, which gate the channel to produce depolarization of the cell membrane.

In the gustatory system, TRPM5 is highly expressed in type II taste receptor cells of the tongue and other taste buds. It plays a central role in signaling sweetness, umami, and bitterness. When tastants bind to G protein-coupled receptors on these cells, a cascade involving gustducin and phospholipase C produces an increase in intracellular calcium. This calcium rise activates TRPM5, leading to cell depolarization, action potential firing, and release of neurotransmitters that convey taste information to gustatory neurons.

Beyond taste, TRPM5 is also expressed in pancreatic beta cells and some enteroendocrine cells, where it contributes to stimulus-secretion coupling and may influence glucose-stimulated insulin release. The channel's structure follows the typical six-transmembrane-domain organization of TRP channels, with the pore formed between the fifth and sixth transmembrane segments and cytoplasmic N- and C- termini.

Genetically, TRPM5 has been a focal point in studies of chemosensation and metabolic regulation. In animals lacking TRPM5, taste responses to sweet, umami, and bitter compounds are markedly reduced or absent, underscoring its essential role in gustation. In humans, genetic variation in TRPM5 can contribute to differences in taste sensitivity and, potentially, metabolic traits related to insulin secretion.