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

Background: Although amiodarone has been referred to as a class III antiarr hythmic agent, it also possesses electrophysiologic characteristics of the three other classes (classes I and TV 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 re flects a pure class IV effect (direct Ca2+ channel inhibition) or a class I I effect (beta -adrenergic receptor blockade) of amiodarone. Methods: In the current study, the effects of amiodarone on Ca2+ current we re studied in the absence of sympathetic regulation using a Xenopus oocyte expression system. The L-type Ca2+ channel alpha (1C) suhunit was coexpress ed with the alpha (2 delta) and beta (2a) subunits in enzymatically digeste d Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte pr eparation. Results: We found that perfusion of 10 muM isoproterenol produced no signif icant 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 sti mulatory sympathetic signal pathway in these oocytes, After 10 minutes of e xposure to 10 muM amiodarone, Ca2+ current amplitude was significantly decr eased 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 muM nifedipine (201 +/- 48 to 108 +/- 48 nA, n=6, P <0.05), a typical Ca2+ channel blocker. On the other hand, neither amiodarone nor n ifedipine significantly altered the Ca2+ current activation or inactivation kinetics. Conclusions: These results demonstrate that amiodarone inhibits Ca2+ curren t in the absence of a functional intrinsic beta -adrenergic stimulatory sys tem and, therefore, represents a true class IV effect.