ROLE OF ATP IN NEUROTRANSMISSION

ATP 在神经传递中的作用

• 批准号: 3414275
• 负责人: ANDRZEJ WIERASZKO
• 金额: $ 12.01万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1990-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414275
• 关键词: adenosine triphosphate; adenosinetriphosphatase; calcium metabolism; corpus striatum; electrical potential; electrophysiology; evoked potentials; extracellular matrix; glutamates; hippocampus; laboratory mouse; laboratory rat; memory; neural facilitation; neural plasticity; neural transmission; neurotransmitter metabolism; neurotransmitters; protein kinase C; synapses

The objectives of the work are to establish the role of ATP in synaptic neurotransmission and synaptic efficiency in the CNS. These studies will be conducted on hippocampal and striatal slices. We recently found a calcium-dependent release of ATP from presynaptic terminals following intense stimulation of Schaffer collaterals (Sch.coll.) in vitro. High frequency stimulation which evokes ATP release simultaneously induced permanent changes in the synaptic efficiency. This phenomenon, called long-term potentiation (LTP), is generally accepted as a good model for testing the properties of memory. Exogenous ATP applied to the hippocampal slices at the concentration observed in the release experiments(nM range) permanently enhanced synaptic efficiency. My hypothesis is that ATP release during intense stimulation triggers changes involved in LTP and may be related to memory formation. The present study will concentrate on two problems : A/further characterization of ATP release mechanism, and B/ the mechanism, through which ATP can potentiate synaptic response. I will determine if the synapses which use different transmitters and have different ability to show LTP (striatal neurons versus hippocampal neurons), release ATP in a similar way. In order to better characterize the metabolism of release ATP, inhibitors and antibody towards ecto-Ca2+- ATPase (the main enzyme responsible for the ATP breakdown in the extracellular space) will be used. In addition, biochemical studies will be conducted to determine if biochemical events observed after electrically evoked LTP evoked potentiation. These studies will be correlated with electrophysiological recordings. The calcium accumulation, release and uptake of endogenous glutamate will be evaluated in the slices incubated with different ATP concentrations. Kinase C regulated by products of phosphoinositol hydrolysis is according to current concepts, a key enzyme engaged in LTP. A suggestion that released ATP can induce LTP by modifying the kinase C activity will be tested. The effect of ATP on synaptic potentials will help find the role of ATP in molecular mechanism of synaptic plasticity and memory.

这项工作的目的是确定ATP在突触中的作用。 中枢神经系统中的神经传递和突触效率。 这些研究将 在海马和纹状体切片上进行。 我们最近发现了一个 突触前末梢钙依赖性释放ATP 强烈刺激Schaffer侧支体外 高 诱发ATP释放的频率刺激 永久性变化 突触的效率。 这种现象，被称为长期 增强（LTP），通常被认为是一个很好的模型来测试 记忆的属性。 外源性ATP应用于海马脑片， 释放实验中观察到的浓度（nM范围） 永久增强突触效率。 我的假设是ATP 在强烈刺激过程中的释放触发了LTP的变化， 可能与记忆的形成有关。 本研究将集中于 两个问题：A/ATP释放机制的进一步表征，和B/ ATP增强突触反应的机制。 我会 确定是否使用不同的发射器的突触， 显示LTP的不同能力（纹状体神经元与海马神经元） 神经元），以类似的方式释放ATP。 为了更好地表征 释放ATP、抑制剂和抗外钙离子抗体的代谢 ATP酶（负责ATP分解的主要酶， 细胞外空间）将被使用。 此外，生物化学研究将 以确定是否观察到生化事件后， 电诱发LTP诱发电位。 这些研究报告将 与电生理记录相关。 钙 将评价内源性谷氨酸的积累、释放和摄取 在不同ATP浓度下培养的切片中。 激酶C 调节磷酸肌醇水解的产物是根据 目前的概念，一个关键酶从事LTP。 一个建议，释放 将测试ATP可通过修饰激酶C活性来诱导LTP。 的 ATP对突触电位的影响将有助于发现ATP在 突触可塑性和记忆的分子机制。