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.