Mechanisms of amiodarone-induced inhibition of Ca2+ current in isolated neonatal rabbit ventricular myocytes.
BACKGROUND
Amiodarone is an effective antiarrhythmic drug used to treat a wide variety of ventricular and supraventricular tachyarrhythmias. Recent voltage clamp studies indicate that amiodarone may possess a variety of antiarrhythmic effects.


METHODS
The tight-seal, whole-cell voltage clamp technique was used to investigate the acute effects of amiodarone on L-type Ca2+ channel kinetics in isolated neonatal ventricular myocytes.


RESULTS
We found that acute perfusion with 1 mumol/L amiodarone inhibited peak inward Ca2+ current by 39.1% (4.85 +/- 0.42 to 2.95 +/- 0.6 pA/pF, n = 10, p < 0.001) without changing the shape of the current-voltage relation. In addition, amiodarone shifted Ca2+ channel steady-state inactivation to more negative membrane potentials. In the absence of amiodarone, half inactivation of the Ca2+ current occurred at a membrane potential of -23.8 +/- 0.2 mV compared to -34.2 +/- 0.6 mV after addition of amiodarone (n = 11, p < 0.01). Furthermore, amiodarone significantly delayed Ca2+ current recovery from previous inactivation.


CONCLUSIONS
These results provide evidence that amiodarone blocks voltage-dependent Ca2+ current in isolated neonatal rabbit ventricular myocytes by a variety of different mechanisms. The inhibitory effect of amiodarone on L-type Ca2+ current may represent an important facet of amiodarone's acute antiarrhythmic activity in the immature heart.
Chen
F
F
University of California at Los Angeles, School of Medicine 90095-7045, USA.
Wetzel
G T
GT
Cho
P
P
Friedman
W F
WF
Klitzner
T S
TS
D000367:Age Factors; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D006352:Heart Ventricles / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D000638:Amiodarone