Unit of Cardiac Physiology, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, 3.14 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, United Kingdom.
Unit of Cardiac Physiology, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, 3.14 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, United Kingdom.
J Mol Cell Cardiol. 2022 Dec;173:61-70. doi: 10.1016/j.yjmcc.2022.08.360. Epub 2022 Aug 28.
Cardiac myocytes rely on transverse (t)-tubules to facilitate a rapid rise in calcium throughout the cell. However, despite their importance in triggering synchronous Ca release, t-tubules are highly labile structures. They develop postnatally, increase in density during exercise training and are lost in diseases such as heart failure (HF). In the majority of settings, an absence of t-tubules decreases function. Here we show that despite reduced t-tubule density due to immature t-tubules, the newborn atrium is highly specialised to maintain Ca release. To compensate for fewer t-tubules triggering a central rise in Ca, Ca release at sites on the cell surface is enhanced in the newborn, exceeding that at all Ca release sites in the adult. Using electron and super resolution microscopy to investigate myocyte ultrastructure, we found that newborn atrial cells had enlarged surface sarcoplasmic reticulum and larger, more closely spaced surface and central ryanodine receptor clusters. We suggest that these adaptations mediate enhanced Ca release at the sarcolemma and aid propagation to compensate for reduced t-tubule density in the neonatal atrium.
心肌细胞依赖于横管（t）来促进细胞内钙离子的快速上升。然而，尽管它们在触发同步钙释放方面非常重要，但 t 管是高度不稳定的结构。它们在出生后发育，在运动训练期间密度增加，并且在心力衰竭（HF）等疾病中丢失。在大多数情况下，t 管的缺失会降低功能。在这里，我们表明，尽管由于不成熟的 t 管导致 t 管密度降低，但新生心房仍然高度特化以维持 Ca 释放。为了弥补触发中央 Ca 上升的 t 管较少，新生细胞表面的 Ca 释放增强，超过了成年人心房所有 Ca 释放部位的 Ca 释放。我们使用电子显微镜和超分辨率显微镜来研究心肌细胞的超微结构，发现新生心房细胞的表面肌浆网增大，表面和中央ryanodine 受体簇更大，间隔更近。我们认为这些适应机制介导了肌膜上增强的 Ca 释放，并有助于传播，以补偿新生儿心房中 t 管密度的降低。
