Effects of CBD on Nav1.4 gating. (a and b) Voltage dependence of activation as normalized conductance plotted against membrane potential in 1 µM CBD (control: V_1/2 = −19.9 ± 4.2 mV, z = 2.8 ± 0.3, n = 5; CBD: V_1/2 = −14.3 ± 4.2 mV, z = 2.8 ± 0.3, n = 5; P > 0.05 for both V_1/2 and z) and normalized activating currents as a function of potential. (c) Voltage dependence of 200 ms (channels were held at −130 mV for 200 ms) F-I curve plotted against membrane potential in 1 µM CBD (control: V_1/2 = −64.1 ± 2.4 mV, z = −2.7 ± 0.3, n = 8; CBD: V_1/2 = −72.7 ± 3.0 mV, z = −2.8 ± 0.4, n = 5; P = 0.0281 for V_1/2 and P > 0.05 for z). (d) Recovery from fast inactivation in 1 µM CBD at 500 ms (control: τ_Fast = 0.0025 ± 0.00069 s, τ_Slow = 0.224 ± 0.046 s; n = 7; CBD: τ_Fast = 0.0048 ± 0.00081 s; τ_Slow = 0.677 ± 0.054 s; n = 5; P = 0.0330 for τ_Fast and P < 0.0001 for τ_Slow). (e) The slow components of recovery from inactivation in control and CBD (1 µM) at 500 ms are shown on the left y axis on a logarithmic scale, and the fraction of slow to fast component of recovery from inactivation is shown on the right y axis. (f) Use-dependent inactivation in control and 2 µM CBD. Normalized current decay plotted as a function of time fitted with an exponential curve (control: τ = 0.14 ± 0.086 s, n = 6; CBD: τ = 0.018 ± 0.0028 s, n = 3; P < 0.05). (g) State-dependent block of peak Nav1.4 current at 10 µM (−110 mV: mean block = 47.3 ± 3.7%, n = 5; %; −70 mV: mean block = 83.8 ± 3.6%, n = 3; *, P = 0.0003). (h) Pulse protocol used for state dependence experiments. Recordings were performed at 1 Hz. Error bars are SE in mean.