Acute effects of amiodarone on sodium currents in isolated neonatal ventricular myocytes: comparison with procainamide.
Recent studies suggest that amiodarone's acute clinical effects in infants and children are related predominantly to its class I antiarrhythmic activity. However, the effects of amiodarone on Na+ currents have not been investigated directly in immature cardiac cells. Accordingly, the tight seal whole cell voltage clamp technique was used to measure time- and voltage-dependent Na+ currents in acutely isolated neonatal ventricular myocytes from 2- to 5-day-old rabbits, before and after addition of amiodarone (0.1-10 microM). To evaluate the class I antiarrhythmic activity of amiodarone in this age group, the effects of amiodarone on Na+ currents were compared with those of procainamide. Similar to procainamide, amiodarone significantly decreased peak inward Na+ current in neonatal ventricular myocytes. Moreover, both amiodarone and procainamide shifted the steady-state inactivation curve to more negative membrane potentials and delayed recovery of the Na+ current from inactivation. Thus, the effects of amiodarone on the Na+ current in immature myocardium are qualitatively similar to those of procainamide, suggesting that amiodarone may act acutely as a class I antiarrhythmic agent in the newborn heart.
Chen
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F
Department of Pediatrics, University of California at Los Angeles, School of Medicine 90024.
Wetzel
G T
GT
Klitzner
T S
TS
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011342:Procainamide / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D016276:Ventricular Function
D015222:Sodium Channels; D012964:Sodium; D011342:Procainamide; D000638:Amiodarone