Inhibition of L-type Ca2+ channel current in Xenopus oocytes by amiodarone.

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 (beta-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 alpha1C subunit was coexpressed with the alpha2delta and beta2a subunits in enzymatically digested Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte preparation.
Results: We found that perfusion of 10 microM 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 microM 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 microM 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 beta-adrenergic stimulatory system and, therefore, represents a true class IV effect.