Afferent output in Type III taste cells involves the classical chemical synapse, wherein Ca2+ entry through voltage-gated (VG) Ca2+-channels triggers Ca2+-dependent exocytosis of a neurotransmitter. In taste bud, extracellular Ca2+ may vary, thus affecting the efficacy of the synaptic transmission. As demonstrated earlier, VG Ca2+ influx and associated intracellular Ca2+ transients were apparently invariant when bath Ca2+ varied in a physiological range. This finding argued that in Type III taste, a mechanism exists to sense variability of extracellular Ca2+ and to provide the proper adjustment of neurotransmission. Previously, we found that extracellular Ca2+-sensing receptor (CaSR) is functionally expressed in Type III cells, where one might serve as a sensor of extracellular Ca2+ and a regulator of activity of VG Ca2+-channels. If so, VG Ca2+-currents and related intracellular Ca2+ signals should have been sensitive to agonists/antagonists of this receptor. In Type III cells dialyzed with CsCl, we detected VG Ca2+-currents. The specific CaSR agonist NPSR-568 suppressed these currents, implicating CaSR in control of their activity. However, the effects of NPSR-568 were apparently instant and irreversible, suggesting its action to be unspecific. NPSR-568 also inhibited VG-currents in Type II cells, wherein CaSR is not expressed. Given this fact and that the other ligands exerted similar inhibitory effects, the effects of CaSR ligands appeared to be unspecific. Since our inhibitory analysis failed, we employed a mathematical model that postulated that extracellular Ca2+ determines VG Ca2+ currents not only as a carrier but also as an CaSR agonist. At certain parameters, the model accurately reproduced the experimental dependence of the VG Ca2+ current on extracellular Ca2+.
2+-sensing receptor, calcium signalization, neurotransmission
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