title: Atrial selectivity in Na+channel blockade by acute amiodarone.
abstract: OBJECTIVE
  Na(+) channel blockers are often used to treat atrial fibrillation (AF), but may sometimes cause ventricular contractile dysfunction. However, amiodarone, a multi-channel blocker with Na(+) channel block, causes less contractile dysfunction. In this study, we tested the hypothesis that Na(+) channel block by amiodarone is selective in atrial myocytes (AM) compared with ventricular myocytes (VM).
  
  
  RESULTS
  Na(+) currents (INa) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodarone inhibited INa in AM (IC50: 1.8 ± 1.1 μM; n = 8) much more than in VM (40.4 ± 11.9 μM; n = 7, P < 0.01). Amiodarone at 10 μM shifted the steady-state inactivation relationship in AM (-16.2 ± 1.7 mV shift, n = 12) compared with VM (-5.9 ± 0.7 mV shift; n = 13; P < 0.01). For mexiletine, the inhibition of INa and inactivation curve shifts were comparable for AM and VM. The effects of amiodarone and mexiletine on conduction velocity (CV) in Langendorff-perfused rabbit hearts were evaluated using an optical mapping system. The decrease of CV by 3 μM amiodarone was significantly larger in the atrium (-18.9 ± 3.8% change; n = 5) compared with the ventricle (-3.7 ± 3.7%; n = 5; P < 0.01). In contrast, mexiletine reduced CV equally in the atrium and the ventricle.
  
  
  CONCLUSIONS
  Amiodarone preferentially inhibits INa of AM compared with VM. Atrial selective Na(+) channel block by amiodarone may contribute to treating AF with less effect on ventricular contractility than other Na(+) channel blockers.
authors: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8401, Japan. tsuzuki@riem.nagoya-u.ac.jp
authors: Tomoyuki
authors: T
authors: Suzuki
authors: Mikio
authors: M
authors: Morishima
authors: Sara
authors: S
authors: Kato
authors: Norihiro
authors: N
authors: Ueda
authors: Haruo
authors: H
authors: Honjo
authors: Kaichiro
authors: K
authors: Kamiya
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D006325:Heart Atria / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D026941:Sodium Channel Blockers; D008801:Mexiletine; D000638:Amiodarone