Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/- mutation in a murine cardiac model

K. Jeevaratnam, Y. Zhang, L. Guzadhur, R. M. Duehmke, M. Lei, A. A. Grace, C. L H Huang

    Research output: Contribution to journalArticlepeer-review


    Aim: To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a+/- mice modelling Brugada syndrome. Methods: Recordings were performed on anaesthetized wild-type (WT) and Scn5a+/- mice and differences attributable to these risk factors statistically stratified. Results: Scn5a+/- exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a +/-. Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a+/-, than the corresponding young male WT and Scn5a+/-. However, PR intervals lengthened with age in male but not in female Scn5a+/- giving the greatest PR intervals in old male Scn5a+/- compared with either old male WT or young male Scn5a +/- mice. In contrast, PR intervals were similar in old female Scn5a+/- and in old female WT. QTc was prolonged in Scn5a +/- compared with WT, and female Scn5a+/- compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a+/-. Thus, T-wave durations were greater in old male Scn5a+/- compared with old male WT, but indistinguishable between old female Scn5a+/- and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. Conclusion: We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a+/-. © 2010 Scandinavian Physiological Society.
    Original languageEnglish
    Pages (from-to)23-33
    Number of pages10
    JournalActa Physiologica
    Issue number1
    Publication statusPublished - Sept 2010


    • age
    • electrophysiology
    • sex
    • sodium channel
    • transgenic mice


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