Lookin Oleg, Khokhlova Anastasia, Myachina Tatiana, Butova Xenia, Cazorla Olivier, de Tombe Pieter
Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russia.
Laboratoire "Physiologie et Médecine Expérimentale du Coeur et des Muscles", Phymedexp, INSERM-CNRS - Montpellier University, Montpellier, France.
Front Physiol. 2022 Apr 4;13:857471. doi: 10.3389/fphys.2022.857471. eCollection 2022.
Cardiomyocytes contract keeping their sarcomere length (SL) close to optimal values for force generation. Transmural heterogeneity in SL across the ventricular wall coordinates the contractility of the whole-ventricle. SL heterogeneity (variability) exists not only at the tissue (macroscale) level, but also presents at the level of a single cardiomyocyte (microscale level). However, transmural differences in intracellular SL variability and its possible dependence on the state of contraction (e.g. end-diastole or end-systole) have not been previously reported. In the present study, we studied three aspects of sarcomere-to-sarcomere variability in intact cardiomyocytes isolated from the left ventricle of healthy guinea-pig: 1) transmural differences in SL distribution between subepi- (EPI) and subendocardial (ENDO) cardiomyocytes; 2) the dependence of intracellular variability in SL upon the state of contraction; 3) local differences in SL variability, comparing SL distributions between central and peripheral regions within the cardiomyocyte. To characterize the intracellular variability of SL, we used different normality tests for the assessment of SL distributions, as well as nonparametric coefficients to quantify the variability. We found that individual SL values in the end-systolic state of contraction followed a normal distribution to a lesser extent as compared to the end-diastolic state of contraction (∼1.3-fold and ∼1.6-fold in ENDO and EPI, respectively). The relative and absolute coefficients of sarcomere-to-sarcomere variability in end-systolic SL were significantly greater (∼1.3-fold) as compared to end-diastolic SL. This was independent of both the transmural region across the left ventricle and the intracellular region within the cardiomyocyte. We conclude that the intracellular variability in SL, which exists in normal intact guinea-pig cardiomyocytes, is affected by the contractile state of the myocyte. This phenomenon may play a role in inter-sarcomere communication in the beating heart.
心肌细胞收缩时会保持其肌节长度（SL）接近产生力量的最佳值。心室壁上SL的跨壁异质性协调着整个心室的收缩性。SL异质性（变异性）不仅存在于组织（宏观尺度）水平，也存在于单个心肌细胞水平（微观尺度）。然而，此前尚未有关于细胞内SL变异性的跨壁差异及其可能对收缩状态（如舒张末期或收缩末期）的依赖性的报道。在本研究中，我们研究了从健康豚鼠左心室分离的完整心肌细胞中肌节间变异性的三个方面：1）心外膜下（EPI）和心内膜下（ENDO）心肌细胞之间SL分布的跨壁差异；2）SL的细胞内变异性对收缩状态的依赖性；3）SL变异性的局部差异，比较心肌细胞中央和周边区域的SL分布。为了表征SL的细胞内变异性，我们使用了不同的正态性检验来评估SL分布，并使用非参数系数来量化变异性。我们发现，与舒张末期收缩状态相比，收缩末期状态下的个体SL值呈正态分布的程度较小（ENDO和EPI中分别约为1.3倍和1.6倍）。与舒张末期SL相比，收缩末期SL的肌节间变异性的相对和绝对系数显著更大（约1.3倍）。这与左心室的跨壁区域和心肌细胞内的区域均无关。我们得出结论，正常完整豚鼠心肌细胞中存在的SL细胞内变异性受心肌细胞收缩状态的影响。这种现象可能在跳动心脏的肌节间通讯中起作用。
