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.