Figure 3.
Gabapentin block of L-type Cav1.2 channel currents expressed in HEK293F cells. (a) Time course of inhibitory effect of 100 µM GBP on Ba2+ currents recorded from HEK cells expressing Cav1.2 channels in combination with either α2δ–1 (i) or α2δ–3 (ii) auxiliary subunits. The averaged fraction of peak current amplitude is plotted against time. Cells were perfused with GBP during the periods indicated by horizontal bars. Inserts correspond to representative macroscopic currents obtained before (black) and after (red) the application of GBP. (iii) The fraction of inhibition after 3 min of drug application is shown as a bar graph. Number of cells examined are indicated in brackets; the asterisk indicates a statistical significance p< 0.05. (b) Normalized current-voltage curves (i) obtained for the recombinant Cav1.2 channel in the presence (red symbols) and in the absence (black symbols) of 100 µM GBP. The values of fitted parameters corresponding to the continuous lines obtained by Boltzmann function fits are shown. Application of GBP produced an average current inhibition of ∼25% with no significant changes in the voltage dependence parameters. Data are plotted as mean ± SEM (n = 5 for each data point). (ii) Typical traces from a representative cell show the effect of GBP on the I-V relationship with no apparent modification of current kinetics.