Xiao Ling, Zhang Liming, Han Wei, Wang Zhiguo, Nattel Stanley
Department of Pharmacology and Therapeutics, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H570-80. doi: 10.1152/ajpheart.01288.2005. Epub 2006 Feb 24.
The female sex is associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. This study examined the hypothesis that sex differences in repolarization may be associated with differential transmural ion-current distribution. Whole cell patch-clamp and current-clamp were used to study ionic currents and action potentials (APs) in isolated canine left ventricular cells from epicardium, midmyocardium, and endocardium. No sex differences in AP duration (APD) were found in cells from epicardium versus endocardium. In midmyocardium, APD was significantly longer in female dogs (e.g., at 1 Hz, female vs. male: 288 +/- 21 vs. 237 +/- 8 ms; P < 0.05), resulting in greater transmural APD heterogeneity in females. No sex differences in inward rectifier K+ current (I(K1)) were observed. Transient outward K+ current (I(to)) densities in epicardium and midmyocardium also showed no sex differences. In endocardium, female dogs had significantly smaller I(to) (e.g., at +30 mV, female vs. male: 2.5 +/- 0.2 vs. 3.5 +/- 0.3 pA/pF; P < 0.05). Rapid delayed-rectifier K+ current (I(Kr)) density and activation voltage-dependence showed no sex differences. Female dogs had significantly larger slow delayed-rectifier K+ current (I(Ks)) in epicardium and endocardium (e.g., at +40 mV; tail densities, female vs. male; epicardium: 1.3 +/- 0.1 vs. 0.8 +/- 0.1 pA/pF; P < 0.001; endocardium: 1.2 +/- 0.1 vs. 0.7 +/- 0.1 pA/pF; P < 0.05), but there were no sex differences in midmyocardial I(Ks). Female dogs had larger L-type Ca2+ current (I(Ca,L)) densities in all layers than male dogs (e.g., at -20 mV, female vs. male, epicardium: -4.2 +/- 0.4 vs. -3.2 +/- 0.2 pA/pF; midmyocardium: -4.5 +/- 0.5 vs. -3.3 +/- 0.3 pA/pF; endocarium: -4.5 +/- 0.4 vs. -3.2 +/- 0.3 pA/pF; P < 0.05 for each). We conclude that there are sex-based transmural differences in ionic currents that may underlie sex differences in transmural cardiac repolarization.
女性与较长的心电图QT间期以及延长QT药物导致的心律失常风险增加相关。本研究检验了复极过程中的性别差异可能与跨壁离子电流分布差异有关这一假设。采用全细胞膜片钳和电流钳技术研究了从犬左心室的心外膜、心肌中层和心内膜分离出的单个心室肌细胞的离子电流和动作电位（AP）。在心外膜和心内膜细胞中未发现动作电位时程（APD）的性别差异。在心肌中层，雌性犬的APD显著更长（例如，在1Hz时，雌性与雄性相比：288±21 vs. 237±8ms；P<0.05），导致雌性的跨壁APD异质性更大。内向整流钾电流（I(K1)）未观察到性别差异。心外膜和心肌中层的瞬时外向钾电流（I(to)）密度也未显示出性别差异。在心内膜，雌性犬的I(to)显著更小（例如，在+30mV时，雌性与雄性相比：2.5±0.2 vs. 3.5±0.3pA/pF；P<0.05）。快速延迟整流钾电流（I(Kr)）密度和激活电压依赖性未显示出性别差异。雌性犬在心外膜和心内膜的缓慢延迟整流钾电流（I(Ks)）显著更大（例如，在+40mV时；尾电流密度，雌性与雄性相比；心外膜：1.3±0.1 vs. 0.8±0.1pA/pF；P<0.001；心内膜：1.2±0.1 vs. 0.7±0.1pA/pF；P<0.05），但在心肌中层I(Ks)未观察到性别差异。雌性犬在所有层面的L型钙电流（I(Ca,L)）密度均大于雄性犬（例如，在-20mV时，雌性与雄性相比，心外膜：-4.2±0.4 vs. -3.2±0.2pA/pF；心肌中层：-4.5±0.5 vs. -3.3±0.3pA/pF；心内膜：-4.5±0.4 vs. -3.2±0.3pA/pF；各层面P<0.05）。我们得出结论，离子电流存在基于性别的跨壁差异，这可能是跨壁心脏复极性别差异的基础。
