The effects of load on transmural differences in contraction of isolated mouse ventricular cardiomyocytes
The effects of load on transmural differences in contraction of isolated mouse ventricular cardiomyocytes
复制标题
DOI：
10.1016/j.yjmcc.2017.12.001
复制
发表时间：
2018-01-01
影响因子：
5
通讯作者：
Solovyova, Olga
中科院分区：
文献类型：
--
作者：
Khokhlova, Anastasia;Iribe, Gentaro;Solovyova, Olga
不同透壁部位心肌细胞在左室壁的力学特性存在差异。心肌细胞的机械环境影响这种异质性，因为机械电反馈机制。在本研究中，我们研究了机械负荷（前负荷和后负荷）对从小鼠左心室分离的心内膜下（ENDO）和心外膜下（EPI）单细胞收缩的跨壁差异的影响。通过轴向拉伸和后负荷（卸载和重载条件）施加的各种预负荷施加到细胞使用碳纤维技术的单个肌细胞。为了模拟实验获得的结果，并预测细胞对负荷变化的反应机制，我们使用了ENDO和EPI细胞的数学模型。我们的主要发现如下：我们的结果表明ENDO和EPI心肌细胞对细胞前负荷变化有不同的机械反应。在低前负荷（未拉伸细胞）的张力性收缩下，ENDO细胞的峰值收缩时间（T-max）和[Ca 2 +]的时间常数;瞬时衰减明显长于EPI细胞。前负荷（拉伸细胞）的增加延长了两种细胞类型的Tmax;然而，EPI细胞的延长幅度更大，导致高前负荷时Tmax的跨壁梯度降低。比较空载和重载（等长）收缩的细胞，我们发现，在收缩的时间过程中的跨壁梯度是独立的负载条件。我们的数学细胞模型能够再现不同的细胞反应的机械负荷的变化时，我们占的ENDO/EPI差异的参数的协同钙激活肌丝的实验结果。
Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of the mechanical load (preload and afterload) on transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various preloads imposed via axial stretch and afterloads (unloaded and heavy loaded conditions) were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Our major findings are the following.Our results show that ENDO and EPI cardiomyocytes have different mechanical responses to changes in preload to the cells. Under auxotonic contractions at low preload (un-stretched cells), time to peak contraction (T-max) and the time constant of [Ca2+); transient decay were significantly longer in ENDO cells than in EPI cells. An increase in preload (stretched cells) prolonged T-max in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in the transmural gradient in Tmax at high preload. Comparing unloaded and heavy loaded (isometric) contractions of the cells we found that transmural gradient in the time course of contraction is independent of the loading conditions. Our mathematical cell models were able to reproduce the experimental results on the distinct cellular responses to changes in the mechanical load when we accounted for an ENDO/EPI difference in the parameters of co-operativity of calcium activation of myofilaments.