Regulation of human heart contractility by essential myosin light chain isoforms
Regulation of human heart contractility by essential myosin light chain isoforms
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DOI：
10.1172/jci118813
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发表时间：
1996-07-15
影响因子：
15.9
通讯作者：
Morano, I
中科院分区：
文献类型：
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作者：
Morano, M;Zacharzowski, U;Morano, I
大多数先天性心脏病患者在右心室表达心房肌球蛋白轻链1 （ALC-1）。我们利用法洛四联症（TOF）、双出口右心室（DORV）和漏斗状肺狭窄（IPS）患者的右心室小窝多细胞脱膜纤维（“皮肤纤维”）研究了ALC-1表达对完整肌体结构中肌球蛋白循环动力学的功能影响。在最大Ca2+激活（pCa 4.5）时，用恒载技术分析了力-速度关系。通过严格监测笼状ATP光解释放后的收缩起始，研究张力发展的半衰期（t(1/2)）。这里调查的患者表达0 - 27%的ALC-1。在正常（0% ALC-1）和病变（19.9% ALC-1）心室中，ALC-1与最大缩短速度（V-max）的相关性有统计学意义，从1.2肌长/秒（ML/s）增加到2.25 ML/秒，增加了1.87倍。随着ALC-1表达量的增加，张力发展的中场时间减少了1.85倍（当ALC-1含量为2%和18.4%时，t（1/2）分别为0.252 s和0.136 s）。我们得出结论，ALC-1在人心脏中的表达调节过桥循环动力学，加速缩短速度和等距张力的产生。
Most of the patients with congenital heart diseases express the atrial myosin light chain 1 (ALC-1) in the right ventricle. We investigated the functional consequences of ALC-1 expression on the myosin cycling kinetics in the intact sarcomeric structure using multicellular demembranated fibers (''skinned fibers'') from the right ventricular infundibulum of patients with Tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and infundibular pulmonary stenosis (IPS). Force-velocity relation was analyzed by the constant-load technique at maximal Ca2+ activation (pCa 4.5). Half-time of tension develoment (t(1/2)) was investigated by monitoring contraction initiation upon photolytic release of ATP from caged-ATP in rigor. The patients investigated here expressed between 0 and 27% ALC-1. There was a statistically significant correlation between ALC-1 and maximal shortening velocity (V-max) which rose 1.87-fold from 1.2 muscle length per second (ML/s) to 2.25 ML/s in a normal (0% ALC-1) and diseased (19.9% ALC-1) ventricle. Halftime of tension development decreased 1.85-fold with increasing ALC-1 expression (t(1/2) was 0.252 s and 0.136 s at 2 and 18.4% ALC-1, respectively). We conclude that the expression of ALC-1 in the human heart modulates crossbridge cycling kinetics accelerating shortening velocity and isometric tension production.