Neurotoxic action of some antiarrhythmic agents: comparative effects of propafenone, lidocaine and amiodarone on leech Retzius nerve cell

Abstract

A series of antiarrhythmic drugs was studied on spontaneous spike activity and depolarizing outward potassium current in leech Retzius nerve cells. Propafenone (0.7 μM/ml) produced a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated after 250 msec by a rapid repolarization. The effect of lidocaine (0.7 μM/ml) on spontaneous spike activity was less pronounced, and early afterdepolarization has been recorded. Amiodarone at the same and much higher concentrations (3 μM/ml) did not generate either a cardiac-like action potential or an early afterdepolarization. In the voltage clamp experiments, fast and slow calcium-activated outward potassium currents were suppressed with propafenone and lidocaine but not with amiodarone. These results suggest that the antiarrhythmic drugs, propafenone and lidocaine modulate calcium-activated potassium channels in leech Retzius nerve cells.