Department of Medicine, Vanderbilt University School of Medicine, 2215B Garland Avenue, Nashville, TN 37232-0575, USA.
Cardiovasc Res. 2012 Aug 1;95(3):300-7. doi: 10.1093/cvr/cvs160. Epub 2012 May 4.
Female gender is a risk factor for long QT-related arrhythmias, but the underlying mechanisms remain uncertain. Here, we tested the hypothesis that gender-dependent function of the post-depolarization 'late' sodium current (I(Na-L)) contributes.
Studies were conducted in mice in which the canonical cardiac sodium channel Scn5a locus was disrupted, and expression of human wild-type SCN5A cDNA substituted. Baseline QT intervals were similar in male and female mice, but exposure to the sodium channel opener anemone toxin ATX-II elicited polymorphic ventricular tachycardia in 0/9 males vs. 6/9 females. Ventricular I(Na-L) and action potential durations were increased in myocytes isolated from female mice compared with those from males before and especially after treatment with ATX-II. Further, ATX-II elicited potentially arrhythmogenic early afterdepolarizations in myocytes from 0/5 male mice and 3/5 female mice.
These data identify variable late I(Na) as a modulator of gender-dependent arrhythmia susceptibility.
女性是长 QT 相关心律失常的危险因素，但潜在机制尚不清楚。在这里，我们测试了假设，即与性别相关的去极化后“晚期”钠电流（I（Na-L））的功能起着作用。
在 Scn5a 基因座被破坏，并用野生型人 SCN5A cDNA 替代的小鼠中进行了研究。在男性和女性小鼠中，基线 QT 间隔相似，但暴露于钠通道 opener 海葵毒素 ATX-II 可引起多形性室性心动过速，而男性为 0/9，女性为 6/9。与男性相比，来自女性小鼠的心肌细胞中的心室 I（Na-L）和动作电位持续时间在 ATX-II 处理前后均增加，尤其是在 ATX-II 处理后增加。此外，ATX-II 可在 0/5 只雄性和 3/5 只雌性小鼠的心肌细胞中引起潜在致心律失常的早期后除极。
这些数据表明，可变的晚期 I（Na）是性别依赖性心律失常易感性的调节剂。
