Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells.

Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells.
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DOI:
10.2741/protasi
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发表时间:
2002-03
期刊:
Frontiers in bioscience : a journal and virtual library
影响因子:
--
通讯作者:
F. Protasi
F. Protasi
中科院分区:
其他
文献类型:
--
作者:
F. Protasi

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肌细胞中的兴奋-收缩(e-c)偶联是一种机制,允许在肌浆网(SR)的Ca 2+释放中转导外膜去极化。由于位于外膜中的电压门控Ca 2+通道二氢吡啶受体(DHPR)和SR的Ca 2+释放通道兰尼碱受体(RyR)之间的相互作用,外膜和内膜之间的通信是可能的。在骨骼肌和心肌细胞中,允许DHPR和RyR相互作用的关键结构元件是它们的附近。然而,这两种分子用于通信的信号在两种肌肉类型中并不相同。在心脏中,在去极化之后,Ca 2+通过DHPR的向内流动触发RyR(钙诱导的钙释放)的开放。另一方面,在骨骼肌中,RyR激活不需要Ca 2 +;相反,两个分子之间的偶联涉及它们之间的直接连接(机械偶联)。超微结构研究表明,功能差异可以解释的差异,在DHPR/RyR相互关联:而这两种蛋白质是非常接近彼此在两个肌肉,DHPR形式四分体只在骨骼纤维。四分体代表结构DHPR/RyR连接,其允许骨骼肌中的Ca 2+非依赖性偶联。
Excitation-contraction (e-c) coupling in muscle cells is a mechanism that allows transduction of exterior-membrane depolarization in Ca2+ release from the Sarcoplasmic Reticulum (SR). The communication between external and internal membranes is possible thanks to the interaction between Dihydropyridine Receptors (DHPRs), voltage-gated Ca2+ channels located in exterior membranes, and Ryanodine Receptors (RyRs), the Ca2+ release channels of the SR. In both skeletal and cardiac muscle cells the key structural element that allows DHPRs and RyRs to interact with each other is their vicinity. However, the signal that the two molecules use to communicate is not the same in the two muscle types. In the heart, the inward flux of Ca2+ through DHPRs, that follows depolarization, triggers the opening of RyRs (calcium induced calcium release). In skeletal muscle, on the other hand, Ca2+ is not needed for RyRs activation; instead the coupling between the two molecules involves a direct link between them (mechanical coupling). Ultrastructural studies show that functional differences can be explained by differences in the DHPR/RyR reciprocal association: whereas the two proteins are very close to each other in both muscles, DHPRs form tetrads only in skeletal fibers. Tetrads represent the structural DHPR/RyR link that allows Ca2+ independent coupling in skeletal muscle.