Wang S Q, Song L S, Lakatta E G, Cheng H
Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Nature. 2001 Mar 29;410(6828):592-6. doi: 10.1038/35069083.
Ca2+-induced Ca2+ release is a general mechanism that most cells use to amplify Ca2+ signals. In heart cells, this mechanism is operated between voltage-gated L-type Ca2+ channels (LCCs) in the plasma membrane and Ca2+ release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The Ca2+ influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release Ca2+ in the form of Ca2+ sparks. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca2+ signal produced by a single opening of an LCC, named a 'Ca2+ sparklet', can trigger about 4-6 ryanodine receptors to generate a Ca2+ spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. This optical analysis of single-channel communication affords a powerful means for elucidating Ca2+-signalling mechanisms at the molecular level.
钙诱导的钙释放是大多数细胞用于放大钙信号的一种普遍机制。在心脏细胞中，这种机制在质膜中的电压门控L型钙通道（LCCs）与肌浆网中通常称为兰尼碱受体的钙释放通道之间起作用。通过LCCs的钙内流穿过由细胞表面和肌浆网膜形成的约12纳米的裂隙，并激活相邻的兰尼碱受体以钙火花的形式释放钙。在这里，我们确定了LCCs与兰尼碱受体之间偶联的动力学、保真度和化学计量。我们表明，由单个LCC开放产生的局部钙信号，称为“钙小火花”，可以触发约4 - 6个兰尼碱受体产生一个钙火花。根据偶联潜伏期的指数分布判断，LCCs与兰尼碱受体之间的偶联是随机的。成功触发火花的小火花比例小于1，并以使用依赖的方式下降。这种对单通道通讯的光学分析为在分子水平阐明钙信号传导机制提供了一种强大的手段。
