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骨骼肌中的兴奋-收缩偶联:最新进展与未解决的问题

Excitation-contraction coupling in skeletal muscle: recent progress and unanswered questions.

作者信息

Shishmarev Dmitry

机构信息

John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.

出版信息

Biophys Rev. 2020 Feb;12(1):143-153. doi: 10.1007/s12551-020-00610-x. Epub 2020 Jan 16.

DOI:10.1007/s12551-020-00610-x
PMID:31950344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7040155/
Abstract

Excitation-contraction coupling (ECC) is a physiological process that links excitation of muscles by the nervous system to their mechanical contraction. In skeletal muscle, ECC is initiated with an action potential, generated by the somatic nervous system, which causes a depolarisation of the muscle fibre membrane (sarcolemma). This leads to a rapid change in the transmembrane potential, which is detected by the voltage-gated Ca channel dihydropyridine receptor (DHPR) embedded in the sarcolemma. DHPR transmits the contractile signal to another Ca channel, ryanodine receptor (RyR1), embedded in the membrane of the sarcoplasmic reticulum (SR), which releases a large amount of Ca ions from the SR that initiate muscle contraction. Despite the fundamental role of ECC in skeletal muscle function of all vertebrate species, the molecular mechanism underpinning the communication between the two key proteins involved in the process (DHPR and RyR1) is still largely unknown. The goal of this work is to review the recent progress in our understanding of ECC in skeletal muscle from the point of view of the structure and interactions of proteins involved in the process, and to highlight the unanswered questions in the field.

摘要

兴奋-收缩偶联(ECC)是一种生理过程,它将神经系统对肌肉的兴奋与肌肉的机械收缩联系起来。在骨骼肌中,ECC由躯体神经系统产生的动作电位引发,该动作电位导致肌纤维膜(肌膜)去极化。这会导致跨膜电位迅速变化,嵌入肌膜的电压门控钙通道二氢吡啶受体(DHPR)会检测到这种变化。DHPR将收缩信号传递给另一个嵌入肌浆网(SR)膜的钙通道——兰尼碱受体(RyR1),RyR1从SR中释放大量钙离子,从而引发肌肉收缩。尽管ECC在所有脊椎动物物种的骨骼肌功能中起着基本作用,但该过程中涉及的两种关键蛋白质(DHPR和RyR1)之间通信的分子机制在很大程度上仍不清楚。这项工作的目的是从该过程中涉及的蛋白质结构和相互作用的角度,综述我们对骨骼肌中ECC理解的最新进展,并突出该领域尚未解决的问题。

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本文引用的文献

1
STAC proteins: The missing link in skeletal muscle EC coupling and new regulators of calcium channel function.STAC 蛋白:在骨骼肌 EC 耦联中的缺失环节和钙通道功能的新调节剂。
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Calcium Channelopathies: Structural Insights into Disorders of the Muscle Excitation-Contraction Complex.钙通道病:肌肉兴奋-收缩复合物疾病的结构见解。
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Allosteric regulators selectively prevent Ca-feedback of Ca and Na channels.变构调节剂选择性地阻止钙和钠通道的钙反馈。
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STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.STAC3 变异导致一种具有独特畸形特征和恶性高热易感性的先天性肌病。
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STAC3 incorporation into skeletal muscle triads occurs independent of the dihydropyridine receptor.STAC3 掺入骨骼肌三联体与二氢吡啶受体无关。
J Cell Physiol. 2018 Dec;233(12):9045-9051. doi: 10.1002/jcp.26767. Epub 2018 Aug 2.
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Duplex signaling by CaM and Stac3 enhances Ca1.1 function and provides insights into congenital myopathy.钙调蛋白和 Stac3 的双信号增强 Ca1.1 功能,并为先天性肌病提供了新的见解。
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Physical interaction of junctophilin and the Ca1.1 C terminus is crucial for skeletal muscle contraction.连接蛋白和 Ca1.1 C 端的物理相互作用对于骨骼肌收缩至关重要。
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Stac proteins associate with the critical domain for excitation-contraction coupling in the II-III loop of Ca1.1.Stac 蛋白与 Ca1.1 的 II-III 环中兴奋-收缩偶联的关键结构域结合。
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STAC proteins associate to the IQ domain of Ca1.2 and inhibit calcium-dependent inactivation.STAC 蛋白与 Ca1.2 的 IQ 结构域结合,抑制钙依赖性失活。
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