Taste buds contain at least 3 types of cells: type I cells appear to have a support (glial-like) function; type II cells are responsible for tasting sweet compounds, bitter compounds, and umami (savoury, amino acid) compounds; and type III cells are responsible for tasting sour (acidic) compounds (reviewed in Liman et al. 2014, Roper and Chaudhari 2017, Kinnamon and Finger 2019, Taruno et al. 2021). Recently identified sodium sensing cells expressing the epithelial sodium channel (ENaC) and POU2F3 are thought to be responsible for tasting low concentrations of salt and may be a subset of type II cells or a novel type of taste cell (Chandrashekar et al. 2010, reviewed in Taruno et al. 2021). High concentrations of salt appear to be detected by both type II and type III cells.
Receptors for sweet compounds, bitter compounds, and umami compounds contain an intracellular domain, transmembrane domains, and an extracellular domain that binds the ligand. The extracellular domains of receptors for sweet and umami ligands have a distinctive "venus flytrap"-shaped domain. Upon binding ligand, sweet taste receptors (TAS1R2:TAS1R3 heterodimers), bitter taste receptors (TAS2R class receptors), and umami receptors (TAS1R1:TAS1R3 heterodimers) then signal through a common downstream pathway: the receptor-ligand complex activates an associated heterotrimeric G protein complex (GNAT3:GNB1 or GNB3:GNG13) to exchange GDP for GTP, the heterotrimeric G protein complex dissociates and the resulting GNB1,3:GNG13 complex activates Phospholipase C beta-2 (PLCB2) which hydrolyzes phosphoinositol 4,5-bisphosphate (PI(4,5)P2) to yield inositol 1,4,5-trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). I(1,4,5)P3 binds and activates ITPR3 to release calcium ions from the endoplasmic reticulum into the cytosol. Cytosolic Ca2+ causes TRPM5 sodium channels to open and depolarize the cell. SCN2A, SCN3A, and SCN9A sodium channels also appear to augment the depolarization. Depolarization causes opening of CALHM1:CALHM3 channels which transport ATP from the cytosol to the extracellular region. ATP then acts as a neurotransmitter in the taste sensing system.
Alternative pathways exist for sensing sugars and glutamate, as evidenced by residual signaling activity in the absence of TAS1R1 or TAS1R3. Glutamate is sensed by the glutamate receptors GRM1 (mGluR1) and GRM4 (mGluR4) expressed in type II taste cells. GRM1 and GRM4 activate calcium channels by an incompletely characterized mechanism that probably involves heterotrimeric G proteins. Glucose may be sensed by a pathway comprising transport into type II taste cells via the glucose transporters SGLT1 and GLUT4, generation of ATP, and inhibition of KATP potassium channels by ATP.
Protons (H+ ions) from acidic compounds translocate from the extracellular region to the cytosol of type III taste cells through the OTOP1 channel. Weak acids such as acetic acid and citric acid are also able to enter type III cells by diffusing through the membrane in their protonated, uncharged forms, Once in the cytosol, the H+ ions inhibit KCNJ2 inwardly rectifying potassium channels, depolarizing the cell. The H+ ions may also open unidentified sodium channels to further depolarize the cell. Depolarization causes exocytosis of the neurotransmitters serotonin (5-HT) and gamma-aminobutyric acid (GABA).
Low concentrations of salt appear to be sensed in specific salt-sensing cells that may be a subset of type II cells. Low concentrations of salt are believed to enter the cell through an epithelial sodium channel (ENaC, SCNN) and the ability to taste low concentrations of salt is dependent on the SCNN1A pore-containing subunit of the SCNN complex in mice. Human taste cells express both SCNN1A and SCNN1D pore-containing subunits. The composition of other subunits of the complex is less certain. The transport of sodium ions (Na+) into the cells depolarizes the plasma membrane and eventually leads to opening of CALHM1:CALHM3 channels which transport ATP from the cytosol to the extracellular region.