Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Am J Physiol Heart Circ Physiol. 2020 Aug 1;319(2):H410-H421. doi: 10.1152/ajpheart.00573.2019. Epub 2020 Jul 10.
Cardiac t tubules undergo significant remodeling in various pathological and experimental conditions, which can be associated with mechanical or osmotic stress. In particular, it has been shown that removal of hyposmotic stress can lead to sealing of t tubules. However, the mechanisms underlying the sealing process remain essentially unknown. In this study we used dextran trapping assay to demonstrate that in adult mouse cardiomyocytes, t-tubular sealing can also be induced by hyperosmotic challenge and that both hypo- and hyperosmotic sealing display a clear threshold behavior requiring ≈100 mosmol/L minimal stress. Importantly, during both hypo- and hyperosmotic challenges, the sealing of t tubules occurs only during the shrinking phase. Analysis of the time course of t-tubular remodeling following removal of hyposmotic stress shows that t tubules become sealed essentially instantly, well before any significant reduction in cell size can be observed. Overall, the data support the hypothesis that the critical event in the process of t-tubular sealing during osmotic challenges is detachment (peeling) of the membrane from the underlying cytoskeleton due to suprathreshold stress. This study provides new insights into how t-tubular membranes respond to osmotic forces. In particular, the data show that osmotically induced sealing of cardiac t tubules is a threshold phenomenon initiated by detachment of t-tubular membrane from the underlying cytoskeleton. The findings are consistent with the hypothesis that final sealing of t tubules is driven by negative hydrostatic intracellular pressure coincident with cell shrinking.
心脏 T 小管在各种病理和实验条件下会发生显著的重塑，这可能与机械或渗透压力有关。特别是，已经表明去除低渗应激可以导致 T 小管的封闭。然而，封闭过程的机制基本上是未知的。在这项研究中，我们使用葡聚糖捕获测定法表明，在成年小鼠心肌细胞中，T 小管的封闭也可以被高渗挑战诱导，并且低渗和高渗封闭都表现出明显的阈值行为，需要 ≈100 mosmol/L 的最小压力。重要的是，在低渗和高渗挑战期间，T 小管的封闭仅发生在收缩阶段。分析去除低渗应激后 T 小管重塑的时间过程表明，T 小管在任何明显的细胞体积减小之前基本上立即被封闭。总的来说，数据支持这样一种假设，即在渗透挑战过程中 T 小管封闭的关键事件是由于超过阈值的压力，膜从下面的细胞骨架上脱离（剥落）。这项研究为 T 小管膜如何响应渗透力提供了新的见解。特别是，数据表明，心脏 T 小管的渗透性诱导封闭是一种由 T 小管膜从下面的细胞骨架上脱离引发的阈值现象。这一发现与这样一种假设是一致的，即 T 小管的最终封闭是由与细胞收缩同时发生的负静水细胞内压力驱动的。
