Type II and Type III taste cells utilize different transduction and signaling mechanisms. Type II cells (left) contain the G protein-coupled taste receptors (TR) for bitter, sweet, and umami taste stimuli. Although the receptors are expressed in different subsets of Type II cells, they all couple to the same downstream signaling cascade, which includes Gβγ activation of phospholipase C β2 (PLCβ2), causing release of Ca2+ from intracellular stores, Ca2+-dependent activation of transient receptor potential cation subfamily M member 5 (TrpM5), membrane depolarization, and release of ATP as a transmitter via an ATP-release channel. Type III cells (right) respond to sour stimuli. While Type II cells signal to afferent fibers by releasing ATP via ATP-permeable channels, Type III cells form conventional synapses and release transmitter via exocytosis. The molecular identity of the ATP release channel and the transmitter composition of the vesicles released by Type III cells at the synapse with the afferent nerve remain important unresolved questions. Other abbreviations: serotonin (5-HT), voltage-gated calcium channel (VGCC), voltage-gated sodium channel (VGNC).