Protasi F, Sun X H, Franzini-Armstrong C
Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Philadelphia 19104-6058, USA.
Dev Biol. 1996 Jan 10;173(1):265-78. doi: 10.1006/dbio.1996.0022.
Muscle fibers release large amounts of calcium from an internal compartment, the sarcoplasmic reticulum (SR), during activation. Two proteins are involved in this process and its control: plasma membrane calcium channels, or dihydropyridine receptors (DHPRs), and SR calcium release channels, or ryanodine receptors (RyRs). The two proteins form part of a structural complex, perhaps unique to muscle cells, which allows an interaction between plasma membrane and SR, resulting in calcium release from the latter. The surface-SR interaction is a step in the coupling between electrical events in the plasma membrane and contraction (excitation-contraction coupling). The structural complexes have been called calcium release units. One key to further understanding the control of calcium homeostasis in muscle is knowledge of how DHPRs and RyRs assemble into calcium release units. We have studied the development of avian myocardium, using immunocytochemistry to locate DHPRs and RyRs and electron microscopy to follow the formation of calcium release units containing feet (RyRs) and large membrane particles (presumably DHPRs). We find that the initial step is a docking of SR vesicles to the plasma membrane, followed by the appearance of feet in the junctional gap between SR and plasma membrane. Feet aggregate in ordered arrays, and the arrays increase in size until they fill the entire junctional gap. Clustering of membrane particles, presumably DHPRs, is apparently coupled to clustering of feet, since the two junction components assemble within patches of membrane of approximately equal size and containing an approximately constant ratio of particles to feet. Thus, despite the fact that no evidence exists for a direct interaction between DHPRs and RyRs in cardiac muscle, some mechanism exists to ensure that the two molecules are clustered in proximity to each other and in the appropriate proportion.
肌肉纤维在激活过程中会从内部隔室肌浆网（SR）释放大量钙。有两种蛋白质参与这一过程及其调控：质膜钙通道，即二氢吡啶受体（DHPRs），以及肌浆网钙释放通道，即兰尼碱受体（RyRs）。这两种蛋白质构成了一种结构复合体的一部分，这种复合体可能是肌肉细胞所特有的，它使得质膜与肌浆网之间能够相互作用，从而导致钙从后者释放。质膜 - 肌浆网的相互作用是质膜电活动与收缩之间耦合（兴奋 - 收缩偶联）过程中的一个步骤。这种结构复合体被称为钙释放单元。进一步理解肌肉中钙稳态调控的一个关键是了解DHPRs和RyRs如何组装成钙释放单元。我们研究了鸡心肌的发育过程，利用免疫细胞化学定位DHPRs和RyRs，并通过电子显微镜观察含有足突（RyRs）和大膜颗粒（可能是DHPRs）的钙释放单元的形成。我们发现初始步骤是肌浆网囊泡与质膜对接，随后在肌浆网与质膜之间的连接间隙中出现足突。足突聚集成有序阵列，并且阵列尺寸不断增大，直到填满整个连接间隙。膜颗粒（可能是DHPRs）的聚集显然与足突的聚集相关联，因为这两个连接成分在大小近似相等且颗粒与足突比例大致恒定的膜片中组装。因此，尽管没有证据表明心肌中的DHPRs和RyRs之间存在直接相互作用，但存在某种机制确保这两种分子彼此靠近并以适当比例聚集。
