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首页> 外文期刊>American Journal of Physiology >cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.
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cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.

机译：cTnT1是一种心肌肌钙蛋白T亚型，可降低肌丝张力并影响左心室压力波形。

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摘要

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT(1), expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1-30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT(1) expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT(1) expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relaxation increased, with hcTnT(1) expression. Substituting total cTnT charge for hcTnT(1) expression resulted in similar conclusions. Morphometric analysis and electron microscopy revealed no differences between wild-type (non-TG) and TG myocardium. No differences in isoform expression of tropomyosin, myosin heavy chain, essential and regulatory myosin light chains (MLC), TnI, or in posttranslational modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results support the hypothesis that cTnT isoform amino-terminal differences affect myofilament function and suggest that hcTnT(1) expression levels present during human development and in human heart disease can affect in vivo ventricular function.
机译：心脏肌钙蛋白T（cTnT）的四种同工型在人类中表达，这是钙依赖性心肌力量发展所必需的蛋白质。它们的电荷和长度不同。它们的表达受到发育的调节，并受疾病状态的影响。人类cTnT（hcTnT）异构体效应已在重组的肌丝中进行了研究。在这项研究中，我们评估了过表达一种cTnT亚型对体外和体内心肌功能的调节作用。 hcTnT亚型hcTnT（1）在发育过程中和心脏病中表达，但在正常成年心脏中不表达，在转基因（TG）小鼠中表达（占总cTnT的1-30％）。皮肤心肌中测得的最大活动张力随相对hcTnT（1）表达的变化而降低。 hCaTnT（1）的表达在半最大力量发展，希尔系数和力量再发展率的pCa没有显着变化。体内最大左心室压力的上升和下降速率降低，并且等容舒张的半衰期增加，并带有hcTnT（1）表达。用总的cTnT电荷代替hcTnT（1）表达得出类似的结论。形态分析和电子显微镜检查显示野生型（非TG）和TG心肌之间无差异。在原肌球蛋白，肌球蛋白重链，必需和调节性肌球蛋白轻链（MLC），TnI或小鼠cTnT，cTnI或调节性MLC的翻译后修饰中均未观察到差异。这些结果支持cTnT亚型氨基末端差异影响肌丝功能的假说，并暗示在人类发育和人类心脏病中存在的hcTnT（1）表达水平会影响体内心室功能。

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