*Lankenau Institute for Medical Research, Wynnewood, PA; and †Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA.
J Cardiovasc Pharmacol. 2017 Sep;70(3):159-167. doi: 10.1097/FJC.0000000000000510.
Late sodium channel current (late INa) is considered to be an antiarrhythmic target. The prime antiarrhythmic mechanisms of late INa inhibition have been suggested to be (1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (through reduction in Cai secondary to the decrease in intracellular sodium [Nai]) and (2) normalization of repolarization. Endogenous late INa is a small current and acceleration of the heart rate decreases late INa density. Late INa influx may significantly contribute to Nai loading, but it seems to largely occur under the combined conditions of augmented late INa density, bradycardia, and prolonged repolarization. At the same time, the relative contribution of late INa (including endogenous) in any type of prolonged cardiac repolarization is critical. Sodium channel blockers inhibit both late INa and peak INa, and a specific block of late INa might be achieved at slow and normal but seems not at rapid activation rates, at which peak INa, a much greater current, is also likely to be inhibited. The antiarrhythmic potential of a specific inhibition of late INa seems to best fit for, or may be limited to, the prevention of arrhythmias associated with prolonged repolarization, but it seems to be applicable to all types of arrhythmic abnormalities with elongated cardiac repolarization.
晚期钠电流（late INa）被认为是一种抗心律失常的靶点。抑制晚期钠电流的主要抗心律失常机制被认为是：（1）抑制细胞内钙介导的节律性活动（通过减少细胞内钠导致的细胞内钙减少）；（2）复极化正常化。内源性晚期钠电流是一种小电流，心率加快会降低晚期钠电流密度。晚期钠内流可能会显著增加钠负荷，但似乎主要发生在晚期钠电流密度增加、心动过缓和复极化延长的联合条件下。同时，晚期钠电流（包括内源性）在任何类型的心脏复极延长中的相对贡献是至关重要的。钠通道阻滞剂抑制晚期钠电流和峰值钠电流，只有在缓慢和正常的激活速率下才能实现晚期钠电流的特异性阻断，而在快速激活速率下似乎不能实现，因为此时也可能抑制峰值钠电流，这是一种更大的电流。特异性抑制晚期钠电流的抗心律失常潜力似乎最适合或仅限于预防与复极化延长相关的心律失常，但似乎也适用于所有类型的心律失常异常，这些异常与心脏复极化延长有关。
