Exposure to the sodium channel opener ATX-II elicited polymorphic ventricular tachycardia in 6 of 9 female mice compared to 0 of 9 male mice, demonstrating that increased late sodium current contributes to gender-dependent arrhythmia susceptibility.
Increased late sodium current in female mice contributes to greater susceptibility to long QT-related arrhythmias compared to males.
Absolute Event Rate: 66.7% vs 0%
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: These data identify variable late I(Na) as a modulator of gender-dependent arrhythmia susceptibility.
Lowe et al. (Fri,) conducted a other in Long QT-related arrhythmia susceptibility (n=18). ATX-II vs. Male mice was evaluated on Polymorphic ventricular tachycardia. Exposure to the sodium channel opener ATX-II elicited polymorphic ventricular tachycardia in 6 of 9 female mice compared to 0 of 9 male mice, demonstrating that increased late sodium current contributes to gender-dependent arrhythmia susceptibility.