Fig. 5

Working hypothesis of TMC4 role in high-concentration salt taste sensation. A Prediction of TMC4 role using taste cell model with (red) or without (black) TMC4. (left) Single action potentials evoked by 2 Hz stimulation with − 140 pA stimulation current (I_stim) for 1 ms. (right) Time derivatives of the voltage (dV_m/dt) during the action potentials. (bottom left) Trains of action potentials evoked by − 15 pA I_stim for 500 ms. (bottom right) Relationship between TMC4 expression level and cycle length. The conductance of TMC4 was amplified by 0 to 3.0, and then trains of action potentials were evoked by − 15 pA I_stim for 500 ms. The averaged cycle length between action potential peaks was plotted against multiplying factor of TMC4 conductance. In all these simulations, the model cell was held at − 70 mV by applying 10 pA holding current (I_hold). [Na⁺]_o = 150 mM, [K⁺]_o = 5.4 mM, [Cl⁻]_o = 150 mM, [Na⁺]_i = 6 mM, [K⁺]_i = 140 mM, [Cl⁻]_i = 30 mM. B Schematic representation of salt taste reception involving TMC4. TMC4 is specifically expressed in high-concentration salt taste cells in the circumvallate papillae (CvP) and the foliate papillae (FoP). TMC4 is not activated at the resting membrane potential. Exposure of the taste cells to high-concentration of NaCl induce depolarization by Na⁺ influx through sodium or cation channels, which triggers action potential for salt taste signals. Furthermore, this depolarization activates TMC4. After depolarization, Cl⁻ influxes the taste cells through the TMC4 and helps the taste cells return to the resting potential. TMC4 consequently may accelerate the cycle of action potentials for salt taste signals. These processes facilitate neurotransmission via high-concentration salt taste cells, with the result that salt taste reception takes place through the glossopharyngeal nerve