Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.
Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.
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DOI：
10.1152/ajpheart.00469.2008
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发表时间：
2008-11
期刊：
影响因子：
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通讯作者：
J. Wasserstrom;S. Kapur;S. Jones;T. Faruque;Rohan Sharma;J. Kelly;Amanda Pappas;Wilson Ho;Alan H. Kadish;G. Aistrup
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文献类型：
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作者：
J. Wasserstrom;S. Kapur;S. Jones;T. Faruque;Rohan Sharma;J. Kelly;Amanda Pappas;Wilson Ho;Alan H. Kadish;G. Aistrup
男性和女性在动作电位波形、离子通道表达模式和心电图特征上表现出明显的差异。然而，目前尚不清楚基于性别的钙循环差异如何导致电生理活动的这些差异。这项研究的目的是调查男性和女性细胞内钙瞬变的差异，并研究这些变化对电生理功能的影响。在3~5个月龄的正常大鼠心脏左室心外膜上观察到了单个心肌细胞内钙离子瞬变的变化。起搏方案被用来测量基础周期长度为500ms和10次S快速起搏序列期间的瞬变特征。女性的钙瞬变幅度比男性小，持续时间长于男性。更重要的是，对于与瞬时持续时间相关的特征，在显微记录部位的心肌细胞之间的钙瞬变特征(异质性指数)，雌性比雄性更大。单个心肌细胞中钙离子交替发育的速率敏感性女性大于雄性，但细胞对雌性交替发育速率依赖性的反应也有更大的异质性。女性的钙瞬变时间越长，恢复的速度也越慢，这可能是导致心率较慢的钙离子和复极交替发生的原因。这些结果表明，雄性和雌性大鼠心脏细胞内钙循环存在明显差异。不仅雌性大鼠对Ca~(2+)的重摄取较慢，而且在微观水平上，Ca~(2+)循环的局部变异性更大。这些基于性别的钙循环差异可能导致男性和女性心电形态和心律失常敏感性的差异。
Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function. Ca2+ transients were measured in individual myocytes within microscopic regions of the fluo-4 AM-loaded left ventricular epicardium of intact rat heart of both sexes (3 to 5 mo old). Pacing protocols were used to measure transient characteristics at a basic cycle length of 500 ms and during 10-s trains of rapid pacing delivered to the left ventricular apex. Ca2+ transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca2+ transient characteristics between myocytes in a microscopic recording site (heterogeneity index) was greater for females than males for characteristics related to transient duration. The rate sensitivity of Ca2+ alternans development in individual myocytes was greater in females than in males, but there was also a greater heterogeneity in cellular responses to the rate dependence of alternans development in females. The longer Ca2+ transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca2+ and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca2+ cycling in male and female rat hearts. Not only is there slower reuptake of Ca2+ in female rats, but there is greater local variability in Ca2+ cycling at the microscopic level. These sex-based differences in Ca2+ cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females.