Gender-related differences in ventricular myocyte repolarization in the guinea pig

Abstract

It is well established that gender-differences exist in cardiac electrophysiology and these are thought to contribute to the increased risk of women, compared to men, for the potentially lethal ventricular arrhythmia, torsades de pointes. Data from animal models with abbreviated estrus cycles suggest that androgens may play a protective role in males. However, the role of female sex hormones in gender-differences in cardiac electrophysiology is less clear. This report describes gender differences in ventricular electrophysiology, investigated using the guinea pig heart. Ionic currents and action potentials were compared between ventricular myocytes isolated from male guinea pig hearts and those from females on the day of estrus (day 0) and 4 days post-estrus (day 4). The density of inward rectifier K(+) current (I(K1)) at -120 mV was significantly greater in male myocytes than in female myocytes either at day 0 or day 4. The peak L-type Ca(2+) current (I(Ca)) at +10 mV was also significantly larger in male myocytes than in day 0 and day 4 female myocytes. Moreover, I(Ca) differed significantly between day 0 and day 4 female myocytes, strongly suggesting that I(Ca) density varies around the estrus cycle. Delayed rectifier (I(K)) tail currents were significantly different between male and female day 4 myocytes. Action potential duration (at 90% repolarization; APD(90)) was significantly shorter in male myocytes than in female myocytes at day 0, but not at day 4, broadly consistent with the combined differences in I(K) and I(Ca) between the three groups. Taken together, our data are consistent with the contribution of multiple factors, rather than a single hormone, to gender differences in ventricular repolarization. Since female guinea pigs possess a conventional estrus cycle, our data suggest that this species may be well suited to elucidating the modulatory influence of ovarian steroids on ventricular repolarization and arrhythmic risk. Our findings suggest that further work examining the basis to gender differences in ventricular repolarization in the guinea pig is warranted.