Published online before print August 16, 2001, doi: 10.1161/hh1701.095644
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Article |
Gender-Based Differences in Cardiac Repolarization in Mouse Ventricle
From the Research Center, Montreal Heart Institute, and Faculty of Pharmacy, University of Montreal, Montréal, Québec, Canada.
Correspondence to Dr Céline Fiset, Research Center, Montreal Heart Institute 5000, Bélanger est, Montréal, Québec, Canada, H1T 1C8. E-mail: fiset{at}icm.umontreal.ca
The mouse heart has become a widely used model for genetic studies of heart diseases. Thus, understanding gender differences in mouse cardiac repolarization is crucial to the interpretation of such studies. The objective of this study was to evaluate whether there are gender differences in cardiac repolarization in mouse ventricle and to gain insights into the ionic and molecular mechanisms underlying these differences. Action potential durations (APDs) and K+ currents in male and female ventricular myocytes were compared using a patch-clamp technique. APD20, APD50, and APD90 were found to be significantly longer in females than males. Examination of the different K+ currents revealed that a significantly lower current density exists in female ventricular myocytes compared with male myocytes for the ultrarapid delayed rectifier K+ current, IKur (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 blots, and confocal analysis that showed a significantly lower expression level of Kv1.5 (coding for IKur) in female compared with male ventricle. The additional K+ currents present in mouse ventricle exhibited no gender differences. In agreement with these electrophysiological data, no differences in the expression levels for the K+ channels underlying these currents were detected 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, IKur, is significantly lower in female mouse ventricle, and as a result, the APD is lengthened.
Key Words: K+ channel • electrophysiology • mouse ventricle • heart • gender
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