Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium
Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium
复制标题
DOI：
10.1085/jgp.201812261
复制
发表时间：
2019-08-01
影响因子：
3.8
通讯作者：
Rangamani, Padmini
中科院分区：
文献类型：
--
作者：
Bell, Miriam;Bartol, Tom;Rangamani, Padmini
树突棘是从神经元的树突突出的小亚室，并且对于信号活动和突触通信是重要的。这些亚隔室的特征是具有不同的形状。虽然已知这些形状与脊柱功能相关，但这些形状-功能关系的具体性质尚未得到很好的理解。在这项工作中，我们系统地研究了形状和大小的脊椎头和脊椎器械，一个专门的内质网隔间内的脊椎头，在调制快速钙动力学的数学建模之间的关系。我们开发了一个空间多室反应扩散模型的钙动力学在三维空间中的各种通量源，包括N-甲基-D-天冬氨酸受体（NMDARs），电压敏感性钙通道（VSCCs），和不同的离子泵的质膜。利用这个模型，我们做出了几个重要的预测。首先，脊柱的体积与表面积之比调节钙动力学。其次，膜通量影响钙动力学的时间和空间上的非线性方式。最后，脊柱装置可以通过充当水槽并重新密封钙浓度来充当钙的物理缓冲器。这些预测为将来树突棘中钙动力学的实验研究奠定了基础。
Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and resealing the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines.