Abstract
The current concept of taste transduction implicates the TASR/PLCβ2/IP3R3/TRPM5 axis in mediating chemo-electrical coupling in taste cells of the type II. While generation of IP3 has been verified as an obligatory step, DAG appears to be a byproduct of PIP2 cleavage by PLCβ2. Here, we provide evidence that DAG-signaling could play a significant and not yet recognized role in taste transduction. In particular, we found that DAG-gated channels are functional in type II cells but not in type I and type III cells. The DAG-gated current presumably constitutes a fraction of the generator current triggered by taste stimulation in type II cells. Bitter stimuli and DAG analogs produced Ca2+ transients in type II cells, which were greatly decreased at low bath Ca2+, indicating their dependence on Ca2+ influx. Among DAG-gated channels, transcripts solely for TRPC3 were detected in the taste tissue, thus implicating this channel in mediating DAG-regulated Ca2+ entry. Release of the afferent neurotransmitter ATP from CV papillae was monitored online by using the luciferin/luciferase method and Ussing-like chamber. It was shown that ATP secretion initiated by bitter stimuli and DAG analogs strongly depended on mucosal Ca2+. Based on the overall findings, we speculate that in taste transduction, IP3-driven Ca2+ release is transient and mainly responsible for rapid activation of Ca2+-gated TRPM5 channels, thus forming the initial phase of receptor potential. DAG-regulated Ca2+ entry through apically situated TRPC3 channels extends the primary Ca2+ signal and preserves TRPM5 activity, providing a needful prolongation of the receptor potential.
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AC performed electrophysiological and imaging experiments, AK and OR assayed ATP release, MB and NK performed the expression analysis and immunostaining, and SK designed the research and wrote the paper. All authors contributed to data analysis and figure design and reviewed the manuscript.
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Cherkashin, A.P., Rogachevskaja, O.A., Khokhlov, A.A. et al. Contribution of TRPC3-mediated Ca2+ entry to taste transduction. Pflugers Arch - Eur J Physiol 475, 1009–1024 (2023). https://doi.org/10.1007/s00424-023-02834-8
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DOI: https://doi.org/10.1007/s00424-023-02834-8