Article Text

Inhibition of L-Type Ca2+ Channel Current in Xenopus Oocytes by Amiodarone
  1. Shulan Ding,
  2. Fuhua Chen,
  3. Thomas S. Klitzner,
  4. Glenn T. Wetzel
  1. From the School of Medicine, University of California at Los Angeles.
  1. Address correspondence to: Glenn Wetzel, MD, PhD, UCLA School of Medicine, 675 C.E. Young Drive South, 3754 MRL, Los Angeles, CA 90095-7045. E-mail gwetzel{at}
  2. This work was presented in an abstract form at the 2000 Western Society of Pediatric Research Regional Meeting.
  3. This work was supported in part by funding from the National Institutes of Health (RR00865), the American Heart Association (93006170), the American Heart Association, Greater Los Angeles Affiliate (1085 GI2), and the Variety Club, J.H. Nicholson Endowment.


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 α 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
  • amiodarone
  • signal pathway
  • Ca2+ channel subunit

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