Shishmarev Dmitry
John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
Biophys Rev. 2020 Feb;12(1):143-153. doi: 10.1007/s12551-020-00610-x. Epub 2020 Jan 16.
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.
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。