Acute and chronic effects of amiodarone on mammalian ventricular cells.
This article reviews experimental studies on the electrophysiological effects of amiodarone on mammalian hearts. Acute application of amiodarone (0.1-10 microM) to papillary muscles or single ventricular cells isolated from rabbits or guinea pigs caused a significant decrease in action potential duration (APD) as well as a marked use-dependent inhibition of the maximum upstroke velocity (Vmax) of action potential with fast recovery kinetics. Acute amiodarone also caused a concentration-dependent decrease in the calcium current (ICa) and the delayed-rectifier potassium current (IK). Action potentials recorded from papillary muscles or single ventricular cells isolated from the rabbits treated with oral amiodarone (100 mg/kg daily, 4 weeks) were characterized by a moderate frequency-independent prolongation of APD. There was no use-dependent Vmax inhibition. The ventricular cells treated with chronic amiodarone showed a significant decrease in the current density of ICa, IK and Ito. The amount of mRNA for Kv1.5, a Shaker-related potassium channel from the rats treated with chronic oral amiodarone was significantly lower than that from control rats. These results suggest that the major and consistent effects of chronic amiodarone is repolarization delay (Class III action) through a decrease in IK and Ito density, probably due to a modulation of gene expression of potassium channels. When amiodarone above a certain concentration is present in the extracellular space, fast kinetic Class I and Class IV actions would be added as acute effects.
Kodama
I
I
Department of Circulation, Nagoya University, Japan.
Kamiya
K
K
Honjo
H
H
Toyama
J
J
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004562:Electrocardiography; D004594:Electrophysiology; D015870:Gene Expression; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000166:cytology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics; D011817:Rabbits; D051381:Rats
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D015221:Potassium Channels; D000638:Amiodarone