Background Although amiodarone has been referred to as a class III antiarrhythmic agent, it also possesses electrophysiologic characteristics of the three other classes (classes I and IV and minor class II effects). Previous studies have demonstrated that amiodarone inhibits Ca2+ channel current in intact cardiac myocytes. However, it is not clear whether this response reflects a pure class IV effect (direct Ca2+ channel inhibition) or a class II effect (β-adrenergic receptor blockade) of amiodarone.
Methods In the current study, the effects of amiodarone on Ca2+ current were studied in the absence of sympathetic regulation using a Xenopus oocyte expression system. The L-type Ca2+ channel α1C subunit was coexpressed with the α2Δ and β2a subunits in enzymatically digested Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte preparation.
Results We found that perfusion of 10 μM isoproterenol produced no significant change in peak Ca2+ current (from 223±33 to 210±29 nA, mean±SEM, n=5, P=not significant), indicating the absence of a functional stimulatory sympathetic signal pathway in these oocytes. After 10 minutes of exposure to 10 μM amiodarone, Ca2+ current amplitude was significantly decreased from 174±33 to 100±26 nA (n=8, P<0.01; control group: 220±33 to 212±29 nA, n=5, P=not significant). These effects were similar to those of 10 μM nifedipine (201±48 to 108±48 nA, n=6, P<0.05), a typical Ca2+ channel blocker. On the other hand, neither amiodarone nor nifedipine significantly altered the Ca2+ current activation or inactivation kinetics.
Conclusions These results demonstrate that amiodarone inhibits Ca2+ current in the absence of a functional intrinsic β-adrenergic stimulatory system and, therefore, represents a true class IV effect.
- antiarrhythmic agent
- Ca2+ current
- signal pathway
- Ca2+ channel subunit
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