| First Author | Lowe JS | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 95 |
| Issue | 3 | Pages | 300-7 |
| PubMed ID | 22562703 | Mgi Jnum | J:202661 |
| Mgi Id | MGI:5520165 | Doi | 10.1093/cvr/cvs160 |
| Citation | Lowe JS, et al. (2012) Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice. Cardiovasc Res 95(3):300-7 |
| abstractText | 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. |
