Neurotoxic action of some antiarrhythmic agents: comparative effects of propafenone, lidocaine and amiodarone on leech Retzius nerve cell.
A series of antiarrhythmic drugs was studied on spontaneous spike activity and depolarizing outward potassium current in leech Retzius nerve cells. Propafenone (0.7 microM/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 microM/ml) on spontaneous spike activity was less pronounced, and early afterdepolarization has been recorded. Amiodarone at the same and much higher concentrations (3 microM/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.
Dekleva
M N
MN
Department of Pathological Physiology, Faculty of Medicine, Belgrade, Serbia.
Beleslin
B B
BB
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D007865:Leeches; D008012:Lidocaine / Q000008:administration & dosage / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D011405:Propafenone / Q000008:administration & dosage / Q000633:toxicity*
D015221:Potassium Channels; D011405:Propafenone; D008012:Lidocaine; D000638:Amiodarone; D011188:Potassium; D002118:Calcium