Protein kinase A modulation of NMDA receptor gating and permeability

蛋白激酶 A 调节 NMDA 受体门控和通透性

基本信息

  • 批准号:
    8634500
  • 负责人:
  • 金额:
    $ 4.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-04-07 至 2015-04-06
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): NMDA receptors are unique from other glutamate receptors in that they are permeable to calcium. This calcium permeability is necessary for neuronal long-term potentiation, the cellular basis of learning and memory, and can also cause excitotoxicity and cell death in disease conditions like stroke and epilepsy. Therefore understanding mechanisms that influence gating and permeability of NMDA receptors will provide more insight to the processes that control plasticity and excitotoxicity. The gating and permeability of NMDA receptors is influenced by a variety of extracellular and intracellular signals, including protein kinase A (PKA), which is the focus of this proposal. PKA has been shown to increase both the amplitude and calcium component of NMDA currents, which then influences many types of neuronal signaling, including long-term potentiation. The mechanism by which PKA modulates NMDA receptors, however, is completely unknown. In this proposal, therefore, modulation of NMDA receptors will be investigated using two aims. The goal of the first aim is to determine the mechanism by which NMDA receptor gating and permeability are modulated by PKA using single NMDA receptor recordings, pharmacological manipulations, kinetic modeling, and site- directed mutagenesis. In the second aim, factors that regulate the modulation of NMDA receptors by PKA will be investigated, including phosphatases and neuromodulators. The results of these experiments will therefore determine the mechanism by which PKA alters NMDA receptor gating and will give insight as to how this modulation interacts with other cellular signals and may ultimately change neuronal output.
说明(申请人提供):NMDA受体不同于其他谷氨酸受体,因为它们对钙离子具有通透性。这种钙渗透性对于神经元的长期增强是必要的,这是学习和记忆的细胞基础,在中风和癫痫等疾病中也会导致兴奋性毒性和细胞死亡。因此,了解影响NMDA受体门控和通透性的机制将为控制可塑性和兴奋性毒性的过程提供更多的信息。NMDA受体的门控和通透性受到多种细胞外和细胞内信号的影响,包括蛋白激酶A(PKA),这是本提案的重点。PKA被证明可以增加NMDA电流的幅度和钙成分,从而影响许多类型的神经元信号,包括长时程增强。然而,PKA调节NMDA受体的机制是完全未知的。因此,在这项提案中,将使用两个AIMS来研究NMDA受体的调节。第一个目标是利用单个NMDA受体记录、药理操作、动力学建模和定点突变来确定PKA调节NMDA受体门控和通透性的机制。在第二个目标中,将研究调节PKA对NMDA受体的调节的因素,包括磷酸酶和神经调节剂。因此,这些实验的结果将确定PKA改变NMDA受体门控的机制,并将深入了解这种调制如何与其他细胞信号相互作用,并最终可能改变神经元的输出。

项目成果

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TERESA K AMAN其他文献

TERESA K AMAN的其他文献

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{{ truncateString('TERESA K AMAN', 18)}}的其他基金

Protein kinase A modulation of NMDA receptor gating and permeability
蛋白激酶 A 调节 NMDA 受体门控和通透性
  • 批准号:
    8315448
  • 财政年份:
    2012
  • 资助金额:
    $ 4.42万
  • 项目类别:
Protein kinase A modulation of NMDA receptor gating and permeability
蛋白激酶 A 调节 NMDA 受体门控和通透性
  • 批准号:
    8458776
  • 财政年份:
    2012
  • 资助金额:
    $ 4.42万
  • 项目类别:
Resurgent Na current: regulation and reconstitution in cultured neurons
复苏的钠电流:培养神经元的调节和重建
  • 批准号:
    7331583
  • 财政年份:
    2007
  • 资助金额:
    $ 4.42万
  • 项目类别:
Resurgent Na current: regulation and reconstitution in cultured neurons
复苏的钠电流:培养神经元的调节和重建
  • 批准号:
    7640759
  • 财政年份:
    2007
  • 资助金额:
    $ 4.42万
  • 项目类别:
Resurgent Na current: regulation and reconstitution in cultured neurons
复苏的钠电流:培养神经元的调节和重建
  • 批准号:
    7454145
  • 财政年份:
    2007
  • 资助金额:
    $ 4.42万
  • 项目类别:

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