Figure 5.

Effects of membrane holding voltage on block of I_Na by 1 μM V102862 in NaIIA-B2 cells. I_Na was elicited by pulsing to 0 mV for 5 ms, either from holding potentials of −120 mV (a) or −63 mV (b) first under control conditions and then in the presence of the drug. (a) At −120 mV, all Na channels are in resting state (see the availability curve in (c)) and V102862 blocks the peak current only by 4%. (b) At −63 mV, about 50% of Na channels are in inactivated state (panel (c)). Current traces were scaled up (scaling factor equals 1.926; note also the difference in the current calibration bars for (a) and (b)) to match the size of the control current at −120 mV. At this voltage, 1 μM V102862 inhibits the peak current by 61%. (c) Steady-state inactivation curve taken in the same cell with a series of 100 ms long conditioning depolarizing prepulses and a 5 ms test pulse to 0 mV. The solid line is the fit of Boltzmann function, 1/{1+exp((V+63.6)/4.81)], where V is the conditioning voltage. (d) Same traces as in (b), but the current trace in the presence of the drug (dotted trace) was scaled up to match the peak of the current in control. The overlap demonstrates that V102862 does not significantly affect either activation or inactivation kinetics of Na⁺ current.