Characterization of ventricular repolarization in male and female guinea pigs

Abstract 

Since both components of the delayed rectifier K⁺ currents (I_Kr and I_Ks) are present in guinea pig and human ventricle, the guinea pig appears as an interesting model to examine the contribution of these currents in sex-related difference of cardiac repolarization. Accordingly, we compared ventricular repolarization in adult male and female guinea pigs using electrophysiological protocols together with Western blots analysis and perfused heart preparation. Our results indicate that there was no sex-related difference in the expression levels of the different K⁺ channels studied (ERG, KvLQT1, minK and Kir2.1), nor in the density of the K⁺ currents (I_Kr, I_Ks and I_K1) encoded by these channels. Action potential durations and QTc intervals were also similar between males and females. In addition, we compared QTc intervals using Langendorff-perfused whole hearts in the presence of I_Kr and/or I_Ks blockers. The I_Kr blocker (5 μM E-4031) prolonged QTc intervals to a similar extent in male (24±2%) and female (29±3%, p=0.1) hearts. Similarly, the degree of QTc prolongation induced by 0.1 μM HMR1556 (I_Ks blocker) was similar in both sexes (males: 15±2% and females 18±2%; p=0.2). In addition to their QT prolonging effects, the I_Kr and I_Ks blockers significantly reduced heart rate in both male and female guinea pigs. These studies clearly demonstrate that adult guinea pigs do not display sex differences in ventricular repolarization.

Keywords: Guinea pig, K⁺ current, Repolarization, Action potential, QT interval, Sex, Heart rate, Ventricle