Ca2 Channels /Pumps /Dependent Signaling Molecules

钙是关键的细胞内信使，但过量的钙是有毒的。本工作研究了大鼠海马区CA1区谷氨酸能轴棘突触中的钙信号。具体地说：1.为了对树突棘中钙离子来源之间相互作用的程度提供结构证据，我们将确定单个树突棘中NMDA受体和电压依赖性钙通道的空间组织。 2.由于CaMKII的酶激活可能对其与钙微区的位置敏感，因此将研究CaMKII在脊柱内的组织结构。 3.[Ca~(2+)]i恢复到静息水平不仅对维持钙信号的保真度很重要，而且对于避免与过量钙负荷相关的潜在细胞毒性也很重要。因此，可能集中在脊椎质膜和细胞器中的钙泵的组织以及可能有助于形成钙瞬变的钙结合蛋白将被研究。这项工作产生的定量解剖数据将用于改进在Mcell程序下运行的计算机模拟，从而更好地洞察树突棘的功能意义。

Calcium is a key intracellular messenger, but excessive levels of Ca 2+ are toxic. This work addresses Ca 2+ signaling in glutamatergic axospinous synapses in the CA1 region of the rat hippocampus. Specifically: 1. To provide structural evidence on the extent of interactions among Ca 2+ sources in dendritic spines, the spatial organization of NMDA receptors and voltage-dependent calcium channels will be determined in individual dendritic spines. 2. Since the enzymatic activation of CaMKII is likely to be sensitive to its location in relationship to Ca 2+ microdomains, the organization of CaMKII within the spine will be studied. 3. Restoration of [Ca2+]i to resting levels is important not only to maintain the fidelity of Ca 2+ signals, but also to avoid the potential cytotoxicity associated with excessive calcium loads. Therefore, the organization of Ca 2+ pumps likely to be concentrated in the plasma membrane and organelles of the spine will be studied, as will calcium-binding proteins that may contribute to shaping Ca 2+ transients. Quantitative anatomical data generated by this work will be used to refine computer simulations running under the MCell program, allowing better insight into the functional significance of dendritic spines.