Fig 2. Metabotropic and sensory TRPs.

a. Metabotropic TRPs couple extracellular cues to biology. Excellular neuroendocrine signals, e. g., neurotransmitters, act on G protein-coupled receptors (GPCRs). Metabotropic TRPs are signal transducers in cells that also express phospholipase (PLC)-dependent GPCRs. Activation of Gq-coupled receptors stimulates PLC activity, which hydrolyze PI(4,5)P₂ into DAG and IP₃. IP₃ then induces Ca²⁺ release from the ER through IP3 receptors. PLC-dependent signal transduction mechanisms activate metabotropic TRPs, as well as store-operated Ca²⁺ entry channels, whose pore-forming subunits are Orai proteins. Details see Table 1. b. Sensory TRPs couple environmental cues to biology. Sensory TRPs are activated by environmental signals such as light, temperature change, osmo-mechanical force, and plant-derived compounds, pain-/itch-inducing chemicals, tastants, and pheromones. These physical and chemical signals activate sensory TRP-mediated Na⁺ entry, increasing the membrane excitability of various sensory cells, including DRG neurons, taste receptor cells, hair cells, and retinal ganglion cells through sensory TRPs. Details see Table 1.