Manfra Ornella, Frisk Michael, Louch William E
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Kirkeveien 166, NO-0407, Oslo, Norway.
Curr Heart Fail Rep. 2017 Jun;14(3):167-178. doi: 10.1007/s11897-017-0329-9.
Membrane invaginations called t-tubules play an integral role in triggering cardiomyocyte contraction, and their disruption during diseases such as heart failure critically impairs cardiac performance. In this review, we outline the growing understanding of the malleability of t-tubule structure and function, and highlight emerging t-tubule regulators which may be exploited for novel therapies.
New technologies are revealing the nanometer scale organization of t-tubules, and their functional junctions with the sarcoplasmic reticulum called dyads, which generate Ca sparks. Recent data have indicated that the dyadic anchoring protein junctophilin-2, and the membrane-bending protein BIN1 are key regulators of dyadic formation and maintenance. While the underlying signals which control expression and localization of these proteins remain unclear, accumulating data support an important role of myocardial workload. Although t-tubule alterations are believed to be a key cause of heart failure, the plasticity of these structures also creates an opportunity for therapy. Promising recent data suggest that such therapies may specifically target junctophilin-2, BIN1, and/or mechanotransduction.
称为横小管的膜内陷在触发心肌细胞收缩中起不可或缺的作用，并且它们在诸如心力衰竭等疾病期间的破坏会严重损害心脏功能。在本综述中，我们概述了对横小管结构和功能可塑性的日益深入的理解，并强调了可能用于新疗法的新兴横小管调节因子。
新技术正在揭示横小管的纳米级组织，以及它们与称为二联体的肌浆网的功能连接，二联体可产生钙火花。最近的数据表明，二联体锚定蛋白连接蛋白-2和膜弯曲蛋白BIN1是二联体形成和维持的关键调节因子。虽然控制这些蛋白质表达和定位的潜在信号仍不清楚，但越来越多的数据支持心肌工作负荷的重要作用。虽然横小管改变被认为是心力衰竭的关键原因，但这些结构的可塑性也为治疗创造了机会。最近有前景的数据表明，此类疗法可能特异性靶向连接蛋白-2、BIN1和/或机械转导。
