The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells
The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells
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DOI：
10.1073/pnas.0306157101
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发表时间：
2004-03-16
影响因子：
11.1
通讯作者：
Cheng, HP
中科院分区：
文献类型：
--
作者：
Wang, SQ;Stern, MD;Cheng, HP
在许多类型的细胞中，胞内Ca 2+释放由兰尼碱受体Ca 2+释放通道（RyRC）介导，RyRC在内质网/肌浆网中组装成二维准晶体阵列。然而，RyRC阵列的原位操作机制是未知的。在这里，我们发现，基本的钙释放事件，钙火花从个别RyRC阵列在大鼠心室肌细胞，表现出量化的钙释放通量。Ca 2+火花的量子特性分析提供了完整细胞中RyRC的单一Ca 2+电流和门控动力学的观点，并揭示了火花激活涉及RyRC的小的可变队列的动态募集。有趣的是，RyRC在多通道火花中的相互作用呈现出一种不寻常的、不可逆的通道门控模式，这是RyRC单独作用所不共享的，也不是体外RyRC所共享的。此外，基于阵列的抑制性反馈，覆盖再生Ca 2+诱导的RyRC的Ca 2+释放，为细胞内Ca 2+信号的微观稳定性提供了超分子机制。
Intracellular Ca2+ release in many types of cells is mediated by ryanodine receptor Ca2+ release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca2+ release events, Ca2+ sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca2+ release flux. Analysis of the quantal property of Ca2+ sparks provided a view of unitary Ca2+ current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca2+-induced Ca2+ release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca2+ signaling.