Roles of voltage-gated Na+ channels in taste cells. Left: sweet, bitter and umami compounds bind to G-protein-coupled receptors (GPCR) present in the apical membrane of type II taste cells. After transduction, Ca2+ is released from internal stores and activates TRPM5 channels (purple). Na+ enters the cell, depolarizes the membrane, and activates voltage-gated Na+ channels (SCN2A, SCN3A, SCN9A; red) to elicit action potentials (red trace). ATP (green dots) is then released through pannexin-1 and/or connexin-based hemichannels (green), where it presumably activates purinergic receptors on afferent nerve fibers and adjacent taste cells (omitted for simplicity). Right: in comparison, type III taste cells are depolarized by sour stimuli (protons), the depolarization possibly involving PKD2L1 channels in the apical membrane. Membrane depolarization activates voltage-gated Na+ channels (SCN2A), causing action potentials (red trace) and Ca2+ influx via voltage-gated (VG) Ca2+ channels (yellow), leading to the release of 5-HT and norepinephrine (blue dots). Whether these biogenic amines activate nerve fibers or modulate adjacent taste cells has not been determined. The tight junction seals adjacent epithelial cells in a narrow band just beneath their apical surface.