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心脏肌球蛋白结合蛋白C(cMyBP-C)是与肌球蛋白紧密结合的粗肌丝元件蛋白,尽管有证据显示 cMyBP-C基因突变常常导致肥厚型心肌病,但cMyBP-c在心肌中的作用相对所知甚少。早期研究表明,牵张激活在心脏收缩中可能有重要作用,基于此,我们在野生型小鼠和我实验室培育的cMyBP-C基因敲除小鼠纯合子(cMyBP-C-／-)的蜕膜心室中,检测了cMyBP-C在牵张激活反应中的作用。在最大或次于最大的 Ca2+活性期对蜕膜心肌细胞的突然牵张,导致收缩力的瞬时升高,该力迅速降为最小,延迟后,力量回复(牵张活化)到大于牵张前力量水平。敲除cMyBP-C显著改变了牵张激活反应,例如,与野生型小鼠心肌相比, 力衰减和延迟性力瞬变速率加快。这些结果提示,cMyBP-C正常抑制了肌球蛋白横桥的空间位置,并轮流限制了横桥与肌动蛋白间的相互作用速率和范围。我们假设敲除cMyBP-C移除了这些约束,增加了横桥与肌动蛋白结合的可能性,提高了牵张后延迟性力回复的速率。不考虑特殊的机制,cMyBP-C-／-心肌细胞中横桥周期的加快可以将这种小鼠中收缩射血的减少解释为心室心肌不成熟牵张激活的一个直接结果。
Cardiac Myosin Binding Protein C (cMyBP-C) is a crude myofilament element protein that binds tightly to myosin. Although there is evidence that mutations in the cMyBP-C gene often lead to hypertrophic cardiomyopathy, cMyBP-c is found in the myocardium The role is relatively poorly understood. Earlier studies have shown that stretch-activation may play an important role in cardiac contractility. Based on this, we detected the cMyBP-C knockout mouse homozygotes (cMyBP-C - / -) in wild-type mice and in our laboratory In the decidual ventricle, the effect of cMyBP-C on the stretch-activated reaction was examined. Sudden distraction of decidual cardiomyocytes during maximal or submaximal Ca2 + activity induces an instantaneous rise in contractility, which is rapidly reduced to a minimum, and after a delay, the strength regains (stretch activation) to a greater extent than before distraction Strength level. Knockout of cMyBP-C significantly altered the stretch-activation response, for example, the rate of force decay and delayed force transients were accelerated compared to wild-type mouse myocardium. These results suggest that cMyBP-C normally suppresses the spatial location of the myosin cross-bridge and in turn limits the rate and extent of cross-bridge-actin interaction. We hypothesized that knocking out cMyBP-C removes these constraints, increasing the possibility of binding of the transverse bridge to actin and increasing the rate of delayed sexual recovery after stretch. Irrespective of the particular mechanism, the accelerated cross-bridge cycle in cMyBP-C - / - cardiomyocytes can account for the reduction in contracting ejection blood in this mouse as a direct result of the distraction activation of the immature myocardium.