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. 1999 Nov;128(5):1011–1020. doi: 10.1038/sj.bjp.0702881

Figure 5.

Figure 5

BW534U87 produced a state-dependent inhibition of recombinant human brain Na+ channels expressed in Chinese hamster ovary cells under voltage-clamp conditions. (A, upper traces) Currents evoked from a holding potential (Vh) of −90 mV to a range of potentials between −80 and +70 mV in control and following application of 10 μM BW534U87. (Lower traces) Peak current-voltage relationship in control and after application of BW534U87 (five cells). (B, Upper traces) Currents evoked at a test potential of 0 mV (3 ms) following a conditioning pulse of −70 or −60 mV (1 s) in control and in 10 μM BW534U87. (Lower traces) Effect of BW534U87 on the voltage-dependence of inactivation. Channels were inactivated by a range of conditioning pulses between −120 to −120 mV (1 s) prior to stepping to a test potential of 0 mV. Data are normalized to the current generated following a −120 mV conditioning pulse. Data were fitted with a Boltzmann function, where in control, the V½; was −62.1±1.8 mV and k was 4.4±0.2 mV/e-fold change. In the presence of 10 μM BW534U87, the V½; was −70.3±1.9 mV and k was 4.6±0.2 mV/e-fold change. (C, Upper traces) Currents evoked by a test pulse to 0 mV (8 ms) from a Vh of −90 or −60 mV (conditioning pulse to −60 mV for 1 s) in control and in 10 μM BW534U87. (Lower traces) Concentration-dependence of inhibition of currents by BW534U87 evoked from a Vh of −90 or −60 mV. The data are normalized with respect to the current amplitudes in the absence of the compound. Each point is the mean±s.e. mean (n=4∼7 cells). The smooth curve was obtained by fitting the data to an independent-binding-site receptor model, from which a half-maximal inhibitory concentration of 10 μM and a Hill coefficient of approximately 1 were estimated. (D) Frequency-dependent inhibition of Na+ currents. Currents were elicited by a train of 20 pulses (3.5 ms duration; 10 Hz) from a Vh of −90 to 0 mV. (Upper traces) Currents evoked by the 1st and 20th pulse in the absence of drug and in presence of 10 μM BW534U87. (Lower traces) Average current amplitude (normalized to the first pulse) during a train of 20 pulses in control and in the presence of 10 μM BW534U87. Data points are the mean±s.e. mean (n=6 cells). Leak currents were not subtracted in these experiments.