Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5gene.[5][6]
TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells. Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K+ and Na+.
TRPM5 is a key component of taste transduction in the gustatory system of bitter, sweet and umami tastes being activated by high levels of intracellular calcium. It has also been targeted as a possible contributor to fat taste signaling.[7][8] The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential.[9]
TRPM5 is expressed in pancreatic β-cells[10] where it is involved in the signaling mechanism for insulin secretion. The potentiation of TRPM5 in the β-cells leads to increased insulin secretion and protects against the development of type 2 diabetes in mice.[11] Further expression of TRPM5 can be found in tuft cells,[12] solitary chemosensory cells and several other cell types in the body that have a sensory role.
Steviol glycosides, the sweet compounds in the leaves of the Stevia rebaudiana plant, potentiate the calcium-induced activity of TRPM5. In this way they stimulate the glucose-induced insulin secretion from the pancreatic β-cell.[11]
Rutamarin, a phytochemical found in Ruta graveolens has been identified as an activator of several TRP channels, including TRPM5 and TRPV1 and inhibits the activity of TRPM8.[14]
Selective blocking agents of TRPM5 ion channels can be used to identify TRPM5 currents in primary cells. Most identified compounds show, however, a poor selectivity between TRPM4 and TRPM5 or other ion channels.
TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility.[15]
Ketoconazole is an antifungal drug that inhibits TRPM5 activity.[16]
^Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID16382100. S2CID17936350.
^Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, Cortés RY, Devantier HR, Jorgensen V, Pawlyk A, Lee SP, Sprous DG, Zhang Z, Bryant R (December 2010). "Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel". Assay and Drug Development Technologies. 8 (6): 703–13. doi:10.1089/adt.2010.0334. PMID21158685.
Islam MS (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN978-94-007-0264-6.
