Inhibition of L-Type Ca2+ Channel Current in Xenopus Oocytes by Amiodarone

BackgroundAlthough 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 i...

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Bibliographic Details
Published in:Journal of investigative medicine 2001-07, Vol.49 (4), p.346-352
Main Authors: Ding, Shulan, Chen, Fuhua, Klitzner, Thomas S., Wetzel, Glenn T.
Format: Article
Language:English
Subjects:
Amiodarone - pharmacology
Animals
Anti-Arrhythmia Agents - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - drug effects
Calcium Channels, L-Type - genetics
Calcium Channels, L-Type - metabolism
Female
In Vitro Techniques
Kinetics
Membrane Potentials - drug effects
Nifedipine - pharmacology
Oocytes - drug effects
Oocytes - metabolism
Patch-Clamp Techniques
Rabbits
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
RNA, Complementary - biosynthesis
RNA, Complementary - genetics
Xenopus
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Summary:BackgroundAlthough 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.MethodsIn 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.ResultsWe 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
ISSN:1081-5589
1708-8267
DOI:10.2310/6650.2001.33900