Fig. 2: THC inhibits nociceptive sodium currents.
A Right: Representative whole-cell voltage-clamp recording of TTX-R sodium currents from acutely dissociated rat nociceptive TG neurons before (upper) and after exposure to THC (10 µM; lower). Currents were elicited by depolarizing steps from a holding potential of −80 mV to 10 mV in 10 mV increments (inset). Left: Concentration-response relationship of TTX-R sodium currents amplitude (normalized to the current before the application of THC) following 4 min of exposure to THC at the indicated concentrations. The solid line represents the fit of the Hill equation. B–C Left: G/Gmax (activation; (B) and I/Imax (availability; (C) curves for TTX-R sodium current before (squares) and 4 min after the application of 10 μM THC (circles). Note that THC induced a rightward shift in activation and a leftward shift in inactivation. To assess the voltage dependence of activation, 100-ms depolarizing steps were applied to a range of test potentials in 10 mV increments, from a holding potential of −80 mV to +30 mV. For the voltage dependence of fast inactivation, a double pulse protocol was used: a prepulse (Vcond) was held constant at 120 ms and its amplitude was varied between −120 and +20 mV. Itest was assessed by stepping to 0 mV for 20 ms. The membrane was held at −80 mV. Right: Box plot and individual paired values of V0.5 of activation (B) and inactivation (C). Paired Student’s t test when **, p ≤ 0.01; ***, p ≤ 0.001. D Left: Voltage-dependence of TTX-R sodium currents steady-state channel availability (Fraction available, I/Imax, plotted as a function of conditioning pulse voltage) before (squares) and 4 min (circles) after the application of 10 μM THC. Vcond was held constant at 10 s, and its amplitude was varied between −120 and 0 mV. 100 ms step to −120 mV was applied before Vtest. Itest was evoked by stepping to +10 mV for 5 ms. The membrane was held at −120 mV. Solid lines: fits to the Boltzmann function. Note a substantial decrease in channel availability following the treatment with THC. Right: Box plot and individual paired values of V0.5 of voltage-dependence of steady-state channel availability before and 4 min after the application of 10 μM THC. Paired Student’s t test when ***, p ≤ 0.001.
