Aims: 

Various clinical and experimental data have identified sex differences in cardiac pathophysiology and incidence of cardiac arrhythmias. The mechanisms responsible for the disparities are still being elucidated. Since gap junction conexin-43 (C ( 43) channels determine myocardial conduction velocity and synchronisation we hypothesized that expression and/or distribution of C ( 43 may differ between males and females.

Methods: 

Experiments were conducted on aged (>1 year-old) male and female Wistar and spontaneously hypertensive (SHR) rats. Ventricular tissue taken from excised hearts was immediately frozen in liquid nitrogen and processed either for immunofluorescence labelling or western blotting of C ( 43 using mouse MAb. Susceptibility to lethal ventricular fibrillation (VF) was examined using isolated heart preparation and electrical burst stimulation or hypokalemic perfusion.

Results: 

Both male and female SHR rats were more vulnerable to VF compared to Wistar counterparts. In correlation, C ( 43 examination revealed that its ventricular tissue expression was significantly lower in hypertensive (SHR) than normotensive (Wistar) rats. In addition, SHR hearts exhibited abnormal myocardial distribution of C ( 43. Comparing to male either SHR or Wistar rat hearts female ones were significantly less susceptible to VF. It correlated with significantly higher C ( 43 expression in females comparing to males.

Conclusion: 

Taken together these findings indicate that the level of myocardial C ( 43 expression is linked with lethal arrhythmia susceptibility and it may help to explain gender-related differences.

Supported by APVV 51- 059505 and 51- 017905.