Taste Cells of the Type III Employ CASR to Maintain Steady Serotonin Exocytosis at Variable Ca 2+ in the Extracellular Medium.

Type III taste cells are the only taste bud cells which express voltage-gated (VG) Ca 2+ channels and employ Ca 2+ -dependent exocytosis to release neurotransmitters, particularly serotonin. The taste bud is a tightly packed cell population, wherein extracellular Ca 2+ is expected to fluctuate markedly due to the electrical activity of taste cells. It is currently unclear whether the Ca 2+ entry-driven synapse in type III cells could be reliable enough at unsteady extracellular Ca 2 . Here we assayed depolarization-induced Ca 2+ signals and associated serotonin release in isolated type III cells at varied extracellular Ca 2+ . It turned out that the same depolarizing stimulus elicited invariant Ca 2+ signals in type III cells irrespective of bath Ca 2+ varied within 0.5-5 mM. The serotonin release from type III cells was assayed with the biosensor approach by using HEK-293 cells co-expressing the recombinant 5-HT4 receptor and genetically encoded cAMP sensor Pink Flamindo. Consistently with the weak Ca 2+ dependence of intracellular Ca 2+ transients produced by VG Ca 2+ entry, depolarization-triggered serotonin secretion varied negligibly with bath Ca 2+ . The evidence implicated the extracellular Ca 2+ -sensing receptor in mediating the negative feedback mechanism that regulates VG Ca 2+ entry and levels off serotonin release in type III cells at deviating Ca 2+ in the extracellular medium.