Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines.
Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines.
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DOI：
10.1371/journal.pone.0002045
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发表时间：
2008-04-30
期刊：
影响因子：
3.7
通讯作者：
Sejnowski TJ
中科院分区：
文献类型：
--
作者：
Keller DX;Franks KM;Bartol TM Jr;Sejnowski TJ
钙进入树突棘可以触发一系列的生化反应，从激活钙调蛋白（CaM）开始，到突触强度的长期变化结束。CaM的激活程度可能取决于局部钙浓度的高度升高和钙浓度短暂增加的持续时间。准确测量钙的这些局部变化是困难的，因为空间太小，分子数量太少。因此，我们开发了一个脊柱内细胞内钙动力学的蒙特卡罗模型，包括钙结合蛋白、钙转运蛋白和由电压和谷氨酸结合激活的离子通道。该模型使用钙指示染料再现了光学记录，结果表明，在没有染料的情况下，细胞内游离钙的瞬态浓度远高于荧光信号预测的浓度。兴奋性突触后电位在突触后密度上诱导了大而持久的钙梯度，从而激活了CaM。当谷氨酸在动作电位发生前10 ms释放时，模拟海马突触增强的活动模式，突触后密度中的钙梯度和CaM的激活远远大于顺序颠倒时，突触强度降低，这可能是诱导突触强度长期变化的机制。这里所展示的选择性CaM激活的时空机制可以用于其他信号通路。
The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM) and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways.
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影响因子：
5.5
作者：
Church, PJ;Stanley, EF
通讯作者：
Stanley, EF
影响因子：
5.5
作者：
Garaschuk, O;Schneggenburger, R;Konnerth, A
通讯作者：
Konnerth, A
影响因子：
16.2
作者：
Holthoff, K;Tsay, D;Yuste, R
通讯作者：
Yuste, R
影响因子：
3.4
作者：
Franks, KM;Bartol, TM;Sejnowski, TJ
通讯作者：
Sejnowski, TJ
DOI：
10.1016/s0006-291x(05)81278-1
发表时间：
1991-10-15
影响因子：
3.1
作者：
EBERHARD, M;ERNE, P
通讯作者：
ERNE, P