Gender-based differences in cardiac repolarization in mouse ventricle

The mouse heart has become a widely used model for genetic studies of heart diseases. Thus, understanding gender differences in mouse cardiac repolari zation is crucial to the interpretation of such studies. The objective of t his study was to evaluate whether there are gender differences in cardiac r epolarization in mouse ventricle and to gain insights into the ionic and mo lecular mechanisms underlying these differences. Action potential durations (APDs) and K+ currents in male and female ventricular myocytes were compar ed using a patch-clamp technique. APD(20), APD(50), and APD(90) were found to be significantly longer in females than males. Examination of the differ ent K+ currents revealed that a significantly lower current density exists in female ventricular myocytes compared with male myocytes for the ultrarap id delayed rectifier K+ current, I-Kat, (at +30 mV. male, 33.2+/-2.9 pA/pF [n= 22]; female, 20.9+/-1.73 pA/pF [n=19], P<0.001). Consistent with these findings were the results of the ribonuclease protection assay. Western blo ts, and confocal analysis that showed a significantly lower expression leve l of Kv1.5 (coding for I-Kur) in female compared with male ventricle. The a dditional K+ currents present in mouse ventricle exhibited no gender differ ences. In agreement with these electrophysiological data, no differences in the expression levels for the K+ channels underlying these currents were d etected between both sexes. This study demonstrates that adult mice exhibit gender differences in cardiac repolarization. The expression of Kv1.5 and of its corresponding K+ current, I-Kur, is significantly lower in female mo use ventricle, and as a result, the APD is lengthened.