Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart.
Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart.
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DOI：
10.1085/jgp.202012860
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发表时间：
2021-11-01
期刊：
影响因子：
--
通讯作者：
Fukuda N
中科院分区：
文献类型：
--
作者：
Kobirumaki-Shimozawa F;Shimozawa T;Oyama K;Baba S;Li J;Nakanishi T;Terui T;Louch WE;Ishiwata S;Fukuda N
心肌细胞的肌节收缩是心脏泵功能的基础。 Kobirumaki-Shimozawa 等人。研究表明，肌节同步性调节肌原纤维动力学，从而调节体内跳动小鼠心脏的节律性肌细胞收缩。心肌细胞中的肌节收缩是心脏泵功能的基础。人们普遍认为，在心肌和骨骼肌中，肌节通过产生相似水平的主动和被动力，在不同负荷下对肌细胞中的肌原纤维动力学做出同样的贡献。在本研究中，我们在 Z 盘中表达 α-肌动蛋白-AcGFP，以分析体内跳动小鼠心脏左心室 (LV) 肌细胞中沿肌原纤维顺序连接的单个肌节的动态行为。为了量化单个肌节对肌原纤维动力学的贡献程度，我们引入了新的参数“贡献指数”（CI）来测量肌节和肌原纤维之间运动的同步性（从-1[完全异步]到1[完全同步]）。首先，肌节之间的 CI 差异显着，正常收缩期间的平均值约为 0.3。其次，当相邻肌节之间的运动是异步的（CI < 0）时，肌节和邻近肌节旁边以及更远的肌节沿着肌原纤维同步移动（CI > 0）。第三，当舒张期和收缩期的左心室压力差（ΔLVP）降低至<10毫米汞柱时，舒张期肌节长度增加。在抑郁状态下，相邻肌节之间的运动明显不同步（CI，-0.3至-0.4），因此，平均CI随着ΔLVP的降低而线性降低。这些发现表明，在体内跳动的小鼠心脏的左心室中，（1）由于相邻肌节之间主动和被动力的不平衡，肌节对肌原纤维动力学的贡献是异质的，（2）在抑郁条件下，力的不平衡是明显的，伴随着被动力的显着增加以及随之而来的肌节之间的拉锯战，（3）通过远端肌节间相互作用的肌节同步性调节心脏的泵血功能与肌原纤维的收缩力相协调。
Sarcomeric contraction in cardiomyocytes serves as the basis for the heart’s pump function. Kobirumaki-Shimozawa et al. show that sarcomere synchrony regulates myofibrillar dynamics and, accordingly, rhythmic myocyte contractions in the in vivo beating mouse heart. Sarcomeric contraction in cardiomyocytes serves as the basis for the heart’s pump functions. It has generally been considered that in cardiac muscle as well as in skeletal muscle, sarcomeres equally contribute to myofibrillar dynamics in myocytes at varying loads by producing similar levels of active and passive force. In the present study, we expressed α-actinin–AcGFP in Z-disks to analyze dynamic behaviors of sequentially connected individual sarcomeres along a myofibril in a left ventricular (LV) myocyte of the in vivo beating mouse heart. To quantify the magnitude of the contribution of individual sarcomeres to myofibrillar dynamics, we introduced the novel parameter “contribution index” (CI) to measure the synchrony in movements between a sarcomere and a myofibril (from −1 [complete asynchrony] to 1 [complete synchrony]). First, CI varied markedly between sarcomeres, with an average value of ∼0.3 during normal systole. Second, when the movements between adjacent sarcomeres were asynchronous (CI < 0), a sarcomere and the ones next to the adjacent sarcomeres and farther away moved in synchrony (CI > 0) along a myofibril. Third, when difference in LV pressure in diastole and systole (ΔLVP) was lowered to <10 mm Hg, diastolic sarcomere length increased. Under depressed conditions, the movements between adjacent sarcomeres were in marked asynchrony (CI, −0.3 to −0.4), and, as a result, average CI was linearly decreased in association with a decrease in ΔLVP. These findings suggest that in the left ventricle of the in vivo beating mouse heart, (1) sarcomeres heterogeneously contribute to myofibrillar dynamics due to an imbalance of active and passive force between neighboring sarcomeres, (2) the force imbalance is pronounced under depressed conditions coupled with a marked increase in passive force and the ensuing tug-of-war between sarcomeres, and (3) sarcomere synchrony via the distal intersarcomere interaction regulates the heart's pump function in coordination with myofibrillar contractility.
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8.8
作者：
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