Copyright © 2004, European Society of Cardiology
Sex and strain differences in adult mouse cardiac repolarization: importance of androgens
Research Center, Montreal Heart Institute, 5000 Rue Bélanger Est, Montréal, Québec, Canada H1T 1C8
Faculty of Pharmacy, University of Montreal Montréal, Québec, Canada H3C 3J7
* Corresponding author. Tel.: +1 514 376 3330 3025; fax: +1 514 376 1355. Email address: celine.fiset{at}icm-mhi.org
Objective: Gender differences in mouse cardiac repolarization have been reported to be due to the stimulatory action of androgens on the ultrarapid delayed rectifier K+ current (IKur) and its underlying Kv1.5 channel. To confirm the regulation of ventricular repolarization by androgens, the present study compared two strains of mice (CD-1 and C57BL/6) that present different androgen levels.
Methods and results: Measurement of testosterone levels in different strains of mice (CD-1, C57BL/6, C3H and FVB) revealed that male C57BL/6 mice had very low levels of testosterone, whereas males of the other strains displayed normal testosterone levels. Furthermore, whole-cell voltage clamp recordings in isolated ventricular myocytes showed that the current density of IKur in male C57BL/6 mice was similar to that in female mice but smaller with respect to male CD-1 mice. Androgen replacement in male C57BL/6 mice as well as in castrated male CD-1 mice shortened ventricular repolarization, increased IKur current density, and increased expression of Kv1.5 channels.
Conclusion: Strain and gender differences observed in mouse cardiac repolarization can be explained by different androgen levels. As a consequence, androgens are major regulatory factors in cardiac repolarization and special attention should be paid to the hormonal status of the animal when studying hormonal regulation of cardiac repolarization.
KEYWORDS Mouse heart; Ventricular repolarization; Mouse strain; K+ current; Kv1.5
Time for primary review 14 days
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