Effects on single channel current: The effect of 3 |J.mol/L GE 70 on single channel kinetics was studied in (S)-DPI 201-106 treated cell-attached patches (n=4). Figure 4 shows recordings from a typical experiment. The amplitude of the single channel current remained unchanged, while average open probability was reduced from 0.70±0.08 to 0.27±0.11 (P<0.05, n=4). The number of sweeps without activity was increased twofold by 3 |J.mol/L GE 70 from 15±5% nulls in control to 33±7% (n=4). Histograms of mean open and closed times (t) were best fitted with two exponentials. The mean open times were decreased (control: T1=3.9±0.5 ms, T2=38.3±4.7 ms; 3 |J.mol/L GE 70: T1=1.7±0.4 ms, P<0.05; T2=12.7±2.9 ms, P<0.05) and mean closed times were increased (control: T1=4.5±1.2 ms, T2=63.8±17.5 ms; 3 |J.mol/L GE 70: T1=5.5±1.6 ms, P>0.1; T2=154.7±22.3 ms, P<0.05) (Figure 5).
Figure 4 Eight consecutive sweeps of original recordings from a cell-attached patch containing one DPI-modified sodium channel (5 fimol/L (S)-DPI 201-106) are shown during control conditions (A) and in presence of3 fimol/L GE 70 (B) in the bathing solution. C,D The corresponding ensemble-averaged currents of202 sweeps each are shown. Depolarizing pulses of400 ms were applied from a holding potential of-100 mV to a test potential of-30 mV at a rate of 2 Hz. The mark at the beginning of each tracing indicates the baseline; downward deflections represent channel openings. The number of records without open channel activity was increased, and closed time between bursts was increased by GE 70
Figure 5 Histograms of mean open (left) and mean closed (right) times are shown during control conditions (A) and in presence of 3 fimol/L GE 70 (B) from the experiment illustrated in Figure 4. Mean open time was decreased by GE 70, while mean closed time was increased
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