首页> 外文期刊>American Journal of Physiology >Maintained contractile reserve in a transgenic mouse model of myocardial stunning.
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Maintained contractile reserve in a transgenic mouse model of myocardial stunning.

机译:在心肌击晕的转基因小鼠模型中保持收缩储备。

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Cardiac excitation-contraction (E-C) coupling is impaired at the myofilament level in the reversible postischemic dysfunction known as "stunned" myocardium. We characterized tension development and calcium cycling in intact isolated trabeculae from transgenic (TG) mice expressing the major proteolytic degradation fragment of troponin I (TnI) found in stunned myocardium (TnI(1-193)) and determined the ATPase activity of myofibrils extracted from TG and non-TG mouse hearts. The phenotype of these mice at baseline recapitulates that of stunning. Here, we address the question of whether contractile reserve is preserved in these mice, as it is in genuine stunned myocardium. During twitch contractions, calcium cycling was normal, whereas tension was greatly reduced, compared with non-TG controls. A decrease in maximum Ca2+-activated tension and Ca2+ desensitization of the myofilaments accounted for this contractile dysfunction. The decrease in maximum tension was paralleled by an equivalent decrease in maximum Ca2+-activated myofibrillar ATPase activity. Exposure to high calcium or isoproterenol recruited a sizable contractile reserve in TG muscles, which was proportionately similar to that in control muscles but scaled downward in amplitude. These results suggest that calcium regulatory pathways and beta-adrenergic signal transduction remain intact in isolated trabeculae from stunned TG mice, further recapitulating key features of genuine stunned myocardium.
机译:在可逆的缺血后功能障碍(称为“震惊的”心肌)中,在肌丝水平上,心脏的兴奋-收缩(E-C)耦合受损。我们表征了完整的分离小梁的张力发展和钙循环,该转基因小鼠来自表达在震惊的心肌(TnI(1-193))中发现的肌钙蛋白I(TnI)的主要蛋白水解降解片段的转基因(TG)小鼠,并确定了从中提取的肌原纤维的ATPase活性TG和非TG小鼠心脏。这些小鼠在基线时的表型概括了令人震惊的表型。在这里,我们要解决的是是否像在真正的震惊心肌中那样在这些小鼠中保留了收缩储备。在抽搐收缩期间,与非TG对照相比,钙循环正常,而张力则大大降低。肌丝的最大Ca2 +激活张力降低和Ca2 +脱敏导致了这种收缩功能障碍。最大张力的降低与最大Ca2 +激活的肌原纤维ATPase活性的等效降低平行。暴露于高钙或异丙肾上腺素在TG肌肉中募集了相当大的收缩储备,与对照组肌肉成比例地相似,但幅度逐渐减小。这些结果表明,钙调节通路和β-肾上腺素信号转导在从震惊的TG小鼠分离的小梁中保持完整,从而进一步概括了真正震惊的心肌的关键特征。

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