The effect of noise on CaMKII activation in a dendritic spine during LTP induction.
The effect of noise on CaMKII activation in a dendritic spine during LTP induction.
复制标题
LTP 诱导过程中噪声对树突棘 CaMKII 激活的影响。
DOI：
10.1152/jn.91235.2008
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发表时间：
2010
影响因子：
2.5
通讯作者：
Holmes,WilliamR
中科院分区：
文献类型：
--
作者：
Zeng,Shangyou;Holmes,WilliamR
长时程增强 (LTP) 诱导过程中钙钙调蛋白依赖性蛋白激酶 II (CaMKII) 的激活是一系列受噪声影响的复杂随机过程。影响树突棘内 CaMKII 激活的噪声有两个主要来源。一种是与 N-甲基-d-天冬氨酸 (NMDA) 受体通道随机开放相关的噪声，另一种是与导致 CaMKII 激活的随机反应扩散动力学相关的噪声。人们已经开发了许多模型来模拟 CaMKII 激活，但还没有完全随机的模型来研究噪声对 CaMKII 激活的影响。在这里，我们构建了一个完全随机模型来研究这些影响。我们的结果表明，噪声对 CaMKII 激活变异性具有重要影响，NMDA 受体通道随机打开的影响比涉及 CaMKII 的随机反应的影响要显着 5-10 倍。此外，CaMKII 激活水平和激活的变异性受到突触 NMDA 受体通道数量微小变化的极大影响。 LTP 诱导方案可能需要强直或重复爆发刺激的原因之一是需要克服固有的变异性，以通过 NMDA 受体通道提供足够大的钙信号；在有意义的生理刺激下，噪声可能会使钙信号超过 CaMKII 激活的阈值，否则它可能不会这样做。
Activation of calcium-calmodulin dependent protein kinase II (CaMKII) during induction of long-term potentiation (LTP) is a series of complicated stochastic processes that are affected by noise. There are two main sources of noise affecting CaMKII activation within a dendritic spine. One is the noise associated with stochastic opening ofN-methyl-d-aspartate (NMDA) receptor channels and the other is the noise associated with the stochastic reaction-diffusion kinetics leading to CaMKII activation. Many models have been developed to simulate CaMKII activation, but there is no fully stochastic model that studies the effect of noise on CaMKII activation. Here we construct a fully stochastic model to study these effects. Our results show that noise has important effects on CaMKII activation variability, with the effect from stochastic opening of NMDA receptor channels being 5–10 times more significant than that from stochastic reactions involving CaMKII. In addition, CaMKII activation levels and the variability of activation are greatly affected by small changes in NMDA receptor channel number at the synapse. One reason LTP induction protocols may require tetanic or repeated burst stimulation is that there is a need to overcome inherent variability to provide sufficiently large calcium signals through NMDA receptor channels; with meaningful physiological stimuli, noise may allow the calcium signal to exceed threshold for CaMKII activation when it might not do so otherwise.