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首页> 外文期刊>American Journal of Physiology >Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T.
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Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T.

机译：Ca（2+）激活从表达R92Q突变型心肌肌钙蛋白T的转基因小鼠心脏的肌丝。

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摘要

The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not well understood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model in which 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca(2+) than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca(2+) (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa(50) caused by increasing the sarcomere length from 1.9 to 2.3 microm was significantly higher for TG than for NTG fibers (DeltapCa(50) = 0.13 +/- 0.01 and 0.29 +/- 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady-state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca(2+) in TG than in NTG fibers (pCa(50) = 5.71 +/- 0.02 and 6.07 +/- 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca(2+) sensitivity in TG myofilaments.
机译：与人类家族性肥厚性心肌病有关的心脏肌钙蛋白T（cTnT）中R92Q突变的功能后果尚不清楚。我们已经研究了转基因（TG）小鼠模型中去污剂去皮纤维束的稳态和稳态前机械活性，在该模型中，心脏中总cTnT的67％被R92Q突变体cTnT取代。 TG纤维比非转基因（NTG）纤维对Ca（2+）更为敏感[半最大活化摩尔Ca（2+）的负对数（pCa（50））= 5.84 +/- 0.01和6.12 +/- 0.01对于NTG和TG纤维]。 TG的肌节长度从1.9微米增加到2.3微米引起的pCa（50）的位移显着高于NTG纤维（对于NTG和TG纤维，DeltapCa（50）= 0.13 +/- 0.01和0.29 +/- 0.02，分别）。 ATP消耗速率与稳态等轴测张力之间的关系是线性的，并且NTG和TG纤维的斜率相同。 TG中的张力重新形成速率对Ca（2+）比NTG纤维更敏感（对于NTG和TG纤维，pCa（50）分别为5.71 +/- 0.02和6.07 +/- 0.02）。我们得出的结论是，总体跨桥循环动力学不会因R92Q突变而改变，但改变的肌钙蛋白-原肌球蛋白相互作用可能是导致TG肌丝中肌丝Ca（2+）敏感性增加的原因。

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