Figure 3.
State-dependent inhibition of Nav current by CBD and effects on recovery from inactivation. A, pulse protocol showing 180 pulses run at 1 Hz at each holding potential and representative current traces. B, CBD potency at four holding potentials at pulse 180 (3 min) (IC50: −100 mV = 12.7 ± 1.0 μm, −90 mV = 10.3 ± 0.5 μm, −80 mV = 6.7 ± 0.4 μm, −70 mV = 2.9 ± 0.6 μm; n = 2–6). C, apparent Kd at different voltages was well fit with a four-state model invoking different potencies for resting and inactivated-state block. D and E, recovery from inactivation in 3.7 μm CBD at: 300 ms (vehicle (Veh): τFast = 0.00173 s, τSlow = 0.0688 s, n = 35; CBD: τFast = 0.00654 s; τSlow = 0.516 s; n = 3) and 10 s (vehicle: τFast = 0.0715 s, τSlow = 0.696 s, n = 33; CBD: τFast = 0.272 s; τSlow = 8.72 s; n = 3). F, the slow components of recovery from inactivation in vehicle and CBD at 300 ms and 3 s are shown on the left y axis, and the fraction of slow to fast component of recovery from inactivation is shown on the right y axis.