NON-NMDA RECEPTORS & CALCIUM CHANNELS IN NEURONS

脊髓的背角是传入感觉的重要部位。 传输到中枢神经元。突触之间的相互作用 受体和电压门控钙通道及其组合 对钙离子内流的影响，尚未在背角神经元或 在中枢神经系统的其他地方。然而，人体的生理效应 [Ca~(2+)]i和钙离子驱动的膜电位变化可能 对两组正常人外周刺激感觉的深刻影响 以及病态。初级神经元之间快速突触传递 传入神经及其背角靶点主要涉及兴奋性 谷氨酸递质，作用于一个或多个突触家族 兴奋性氨基酸(EAA)受体称为NMDA，而非NMDA或 红藻氨酸和奎尼酸受体。EaaS将通过以下方式使细胞去极化 激活这些受体并间接激活VGCC导致[Ca~(2+)]i 从而使膜电位变得更加去极化。这种形式的 相互作用意味着钙依赖电位的突触激活 膜电位变化和膜电位变化的高度非线性增强 [Ca~(2+)]I.最近的实验也表明，红藻氨酸激活 存在对钙离子具有通透性的受体操作通道(ROCs)。如果这些都在 背角神经元，它可以完全改变定位、动力学 突触激活过程中钙离子进入的电压依赖性。最后， 代谢偶联的非NMDA受体的可能性 在背角神经元的突触传递中所起的作用尚未得到检验。 因此，钙离子内流的调节将在非NMDA之后进行研究 受体激活以确定1)钙离子是否通过非NMDA进入 受体的发生，2)VGCC属性对决定 诱发的[Ca~(2+)]i瞬变的幅度和时间进程及3)作用 非NMDA受体介导的[Ca~(2+)]i变化 同时测定[Ca~(2+)]i和膜电位的变化 特别是关于钙离子进入是否是由于钙离子- 依赖动作电位或VGCC持续开放。树枝状 将使用微光视频研究受体和通道属性 用于良好空间分辨率的成像和用于良好时间的光电倍增管 决议。这样的研究将提高我们对该复合体的理解 通常发生在突触输入和VGCC之间的相互作用 后角。此外，[Ca~(2+)]i的变化也牵涉到 突触传递的活动依赖的易化过程 这可能是病理性疼痛综合征如痛觉过敏的基础。最后， 由于EAA介导的脊髓神经元[Ca2+]i持续升高 与脊髓损伤后继发性细胞死亡相关 这些实验可能会提高对损伤的基本认识 与细胞死亡相关的机制。

The dorsal horn of the spinal cord is an important site of afferent sensory transmission to central neurons. Interactions between the synaptic receptors and voltage-gated calcium channels (VGCCs), and their combined effects on Ca2+ entry, have not been well studied in dorsal horn neurons or elsewhere in the central nervous system. Yet the physiological effects of [Ca2+]i and calcium-driven changes in membrane potentials could have profound influence on the sensation of peripheral stimuli in both normal and pathological states. Fast synaptic transmission between primary afferents and their dorsal horn targets primarily involves an excitatory transmitter, glutamate, acting on one or more of a family of synaptic excitatory amino acid (EAA) receptors known as the NMDA, and non-NMDA or kainate and quisqualate receptors. EAAs will depolarize the cells by activation of these receptors and indirectly activate VGCCs causing [Ca2+]i to elevate and membrane potential to become more depolarized. This form of interaction implies synaptic activation of Ca2+-dependent potentials with highly nonlinear boosting of both the change in membrane potential and [Ca2+]i. Recent experiments have also suggested that kainate-activated receptor operated channels (ROCs) permeable to Ca2+ exist. If these are in dorsal horn neurons, it could completely change the localization, kinetics and voltage dependence of Ca2+ entry during synaptic activation. Finally, the possibility of a non-NMDA receptor that is metabolically coupled having a role in synaptic transmission in dorsal horn neurons is untested. Therefore, the regulation of Ca2+ entry will be studied following non-NMDA receptor activation to determine 1) if Ca2+ entry through the non-NMDA receptors occurs, 2) the contribution of VGCC properties to determining the amplitude and time course of the evoked [Ca2+]i transient and 3) the role of Ca2+ release in non-NMDA receptor mediated changes in [Ca2+]i. Simultaneous measurement of [Ca2+]i and membrane potential changes should be particularly informative about whether Ca2+ entry is due to Ca2+- dependent action potentials or sustained opening of VGCCs. Dendritic receptor and channel properties will be studied using low light level video imaging for good spatial resolution and photomultiplier tubes for good time resolution. Such studies will improve our understanding of the complex interactions that normally occur among synaptic inputs and VGCCs in the dorsal horn. Furthermore changes in [Ca2+]i have been implicated in processes of activity dependent facilitation of synaptic transmission such as might underlie pathological pain syndromes like allodynia. Finally, since sustained EAA-mediated elevation of [Ca2+]i in spinal cord neurons is associated with secondary cell death following traumatic spinal cord injury, these experiments may improve the basic understanding of the mechanisms associated with cell death.