Figure 5.

Amitriptyline-induced use-dependent block and concentration-dependent block of fast sodium current (I_Na) but not transient outward potassium channel current (I_to). (A) Simultaneous measurements of fast I_Na and I_to during the first pulse and 40th pulse (steady state) in control solution (left panel) and 6 min after addition of 0.2 μM amitriptyline (right panel). (B) Bar graph of I_Na and I_to of the first pulse and 40th pulse (steady state) in the presence of 0.2 μM and 0.5 μM amitriptyline normalized to control values (average ± SEM, n = 6). (C) Time controls in the absence of drug. Pulse trains were elicited repeatedly over a time course of 10 min. First pulse and steady state currents during the last train of the 10 min period were measured as a fraction of the currents during the first train (average ± SEM, n = 6). (D) Current-voltage relation showing voltage control during activation of sodium channels at 37°C in reduced external sodium. I_Na was recorded in potassium-free solution containing 40 mM NaCl and 0.3 mM CdCl₂. Top, voltage template. Middle, currents recorded in drug-free solution. Bottom, the current-voltage relation shown for the traces above.