Schematic diagram showing molecular mechanisms for sweet detection via TAS1Rs in taste cells. The binding of sweeteners to TAS1R2/TAS1R3 activates a trimeric G-protein (Gα-gustducin, Gβ1 or Gβ3, and Gγ13) and phospholipase Cβ2 (PLCβ2). Then, inositol-1,4,5-trisphosphate (IP3) is produced, and [Ca2+]i is increased by Ca2+ release from Ca2+ store. Ca2+ activates the transient receptor potential channel M5 (TRPM5), leading to cell depolarization and the firing of action potentials (APs) via voltage-gated sodium channels (VGSCs). Then, ATP-permeable CALHM1/3 opens to secrete ATP from the taste cell.