Fig. 1
Effect of safinamide (SAF) on the voltage-gated Na+ current (INa) in pituitary tumor (GH3) cells. To record macroscopic currents, calcium ion–free Tyrode’s solution containing 10 mM tetraethylammonium chloride and 0.5 mM cadmium chloride was added to the cells; the recording electrode was filled with solution containing cesium ions. (A) Current traces during the control period (a, black; untreated cells) and during exposure to 10 (b, blue) and 30 (c, red) μM SAF. The voltage-clamp protocol used is indicated atop the current traces. In panel A, the third graph from the top is an expanded version the second graph (purple dashed box). (B) Time course showing effect of 10 and 30 μM SAF on the amplitude of peak INa. Each Current amplitude (indicated with black circles) was measured at the beginning of depolarizing pulse at a rate of 2 Hz. Horizontal bar shown above indicates the SAF application. (C) Concentration–response curves corresponding to SAF-mediated stimulation of transient INa [(INa(T)): blue filled squares] and late INa [INa(L); sustained: red open circles] in GH3 cells (mean ± standard error of the mean; n = 8 for each point). The current amplitude was measured at the beginning and end of a 30-ms depolarizing pulse (−100 to −10 mV). The gray smooth line indicates the goodness of fit of our model to the modified Hill equation. The EC50 values corresponding to the SAF-induced stimulation of INa(T) and INa(L) were 27.1 and 4.8 μM, respectively (least-squares minimization)