August 10, 2012

Key to a woman’s heart (condition)?

Females may be at higher risk of potentially fatal heart condition due to gender differences in a protein involved in the heart’s electrical activity.


Long QT syndrome (LQTS), characterized by a prolonged QT interval – part of the heart’s electrical cycle measured on an electrocardiogram – is associated with potentially fatal arrhythmias. Women are at higher risk of experiencing these LQTS-associated arrhythmias, but the mechanisms underlying this gender difference are not clear. Mutations in 13 genes, including the cardiac sodium channel gene SCN5A, that underlie the heart’s electrical currents have been identified in this disease.

Dan Roden, M.D., assistant vice chancellor for Personalized Medicine, and colleagues replaced the mouse version of the SCN5A gene with the human version and examined the impact of gender on sodium channel function. They found that while baseline QT intervals were similar in male and female mice, exposure to a toxin that targets the channel led to an irregular heart rhythm in female mice only. The researchers also showed striking gender differences in cellular measures of electrical activity.

The findings, reported in the Aug. 1 issue of Cardiovascular Research, suggest that gender-dependent differences in this sodium current (called the “variable INa-L”) may underlie females’ increased susceptibility to these arrhythmias.

The research was supported by a grant from the National Heart Lung and Blood Institute (HL049989) of the National Institutes of Health.