Calcium channels in evoked neurotransmitter release at individual synapses and neurological disease

个体突触诱发神经递质释放的钙通道和神经系统疾病

• 批准号: G0600089/1
• 负责人: Kirill Volynski
• 金额: $ 132.59万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600089%2F1
• 关键词: Calcium; channels; evoked; neurotransmitter; release

Synapses between neurons are critical sites of modulation and plasticity, both in health and in disease. We have devised a new way of investigating the events leading up to the release of chemical neurotransmitters at individual synapses. This is based on measuring, with fluorescence microscopy, rapid changes in the concentration of calcium ions, as well as the rate at which small vesicles containing chemical neurotransmitters are discharged. This approach will allow us to investigate how different channels that transmit calcium ions into the terminal control the release of vesicles, how they influence plasticity, and how synapses are influenced by other modulatory neurotransmitters acting upon presynaptic terminals. Moreover, it has recently been established that some inherited cases of migraine, ataxia (incoordination caused by abnormal cerebellar function) and epilepsy are due to mutations of one subtype of calcium channel. We will apply these novel methods to investigate how the desiase-linked mutations affect calcium signals in nerve terminals, and how they affect neurotransmitter release. By making advances at the cutting edge of basic neuroscience relevant to neurological disease this project may point the way to new approaches of treating several disabling neurological diseases caused by intermittent disturbances of synaptic function.

神经元之间的突触是调节和可塑性的关键部位，无论是在健康还是在疾病中。我们设计了一种新的方法来研究导致单个突触释放化学神经递质的事件。这是基于荧光显微镜测量钙离子浓度的快速变化，以及含有化学神经递质的小泡的释放速率。这种方法将使我们能够研究不同的通道，将钙离子传输到终端控制囊泡的释放，它们如何影响可塑性，以及突触如何受到其他调节神经递质作用于突触前终端的影响。此外，最近已经确定，一些遗传性偏头痛、共济失调（由小脑功能异常引起的不协调）和癫痫的病例是由于钙通道的一种亚型的突变。我们将应用这些新的方法来研究如何desiase-linked突变影响神经末梢的钙信号，以及它们如何影响神经递质的释放。通过在与神经系统疾病相关的基础神经科学前沿取得进展，该项目可能为治疗由突触功能间歇性紊乱引起的几种致残性神经系统疾病指明新的方法。