Atrial selectivity in Na+ channel blockade by acute amiodarone
Atrial selectivity in Na+ channel blockade by acute amiodarone
复制标题
DOI：
10.1093/cvr/cvt007
复制
发表时间：
2013-04-01
影响因子：
10.8
通讯作者：
Kamiya, Kaichiro
中科院分区：
文献类型：
--
作者：
Suzuki, Tomoyuki;Morishima, Mikio;Kamiya, Kaichiro
钠通道阻滞剂常用于治疗心房颤动（AF），但有时可能导致心室收缩功能障碍。然而，胺碘酮，一种具有Na通道阻滞的多通道阻滞剂，引起较少的收缩功能障碍。本研究采用全细胞膜片钳技术检测了家兔心房肌细胞（AM）和心室肌细胞（VM）的钠通道电流（I-Na），以验证胺碘酮对心室肌细胞（VM）钠通道阻滞的选择性。胺碘酮对AM中I-Na的抑制作用（IC 50：1.8 1.1 M; n 8）远大于VM中的抑制作用（40.4 11.9 M; n 7，P 0.01）。与VM（5.9 ± 0.7 mV偏移; n 13; P 0.01）相比，10 M胺碘酮偏移了AM（16.2 ± 1.7 mV偏移，n 12）中的稳态失活关系。对于美西律，AM和VM对I-Na的抑制作用和灭活曲线移动相当。应用光学标测系统观察胺碘酮和美西律对Langendorff灌流兔心传导速度（CV）的影响。与心室（3.7 3.7; n 5; P 0.01）相比，心房（18.9 3.8变化; n 5）中3 M胺碘酮引起的CV降低显著更大。胺碘酮优先抑制AM的I-Na，而不是VM。胺碘酮的心房选择性钠通道阻滞可能有助于治疗房颤，对心室收缩力的影响小于其他钠通道阻滞剂。
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).Na currents (I-Na) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodarone inhibited I-Na in AM (IC50: 1.8 1.1 M; n 8) much more than in VM (40.4 11.9 M; n 7, P 0.01). Amiodarone at 10 M 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 I-Na 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 M 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.Amiodarone preferentially inhibits I-Na 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.