Unit of Cardiac Physiology, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom; email:
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
Annu Rev Physiol. 2022 Feb 10;84:229-255. doi: 10.1146/annurev-physiol-061121-040148. Epub 2021 Nov 15.
In mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent work has provided a newfound appreciation of the plasticity of the t-tubule network's structure and function. Indeed, t-tubules are now understood to support dynamic regulation of the heartbeat across a range of timescales, during all stages of life, in both health and disease. This review article aims to summarize these concepts, with consideration given to emerging t-tubule regulators and their targeting in future therapies.
在哺乳动物心肌细胞中，细胞质膜包括表面的肌质膜，但也包括一个称为横管（t-管）的膜内陷网络。这些结构将动作电位深入细胞内部，允许有效的 Ca 释放触发和收缩起始。虽然过去认为它们只是兴奋-收缩耦联的静态促进者，但最近的研究工作对 t-管网络结构和功能的可塑性有了新的认识。事实上，现在已经了解到，t-管在生命的各个阶段，在健康和疾病状态下，都能支持心跳在多个时间尺度上的动态调节。这篇综述文章旨在总结这些概念，并考虑新兴的 t-管调节剂及其在未来治疗中的靶向性。
