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PubMed 22562703


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Title: Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice.

Authors: John S Lowe, Dina Myers Stroud, Tao Yang, Lynn Hall, Thomas C Atack, Dan M Roden

Journal, date & volume: Cardiovasc. Res., 2012 Aug 1 , 95, 300-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22562703


Abstract
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.