PROPERTIES AND REGULATION OF GLUTAMATE RECEPTORS

L激活的一类神经递质受体分子--谷氨酸 似乎在脊椎动物中介导了最快的突触传递 中枢神经系统。这里描述的项目的总体目标是 是为了加深我们的药理学和生物物理学方面的理解 重要的一类受体被激活和调节。 谷氨酸受体在几乎每一类正常的中枢神经系统中发挥作用 神经系统活动。有证据表明他们参与了所有 感觉系统，通常处于多个层次，从感觉器官到 皮质关联区。谷氨酸反应的存在 小脑、纹状体和脊髓提示广泛参与 马达系统。谷氨酸受体在大脑皮质中密度很高。 似乎对学习和学习等高级功能是必不可少的 记忆。一组与正常大脑深度相关的受体类型 功能也可以在大脑功能障碍中发挥重要作用；谷氨酸 受体与许多脑部疾病的病因有关。 包括癫痫，阿尔茨海默氏症，亨廷顿氏症，以及 精神分裂症。此外，低氧诱导神经元死亡，作为一种 例如，中风的后果可能是过度激活引起的 谷氨酸受体。 对正常或病理性脑功能的描述将需要 详细了解谷氨酸受体是如何工作的。这项研究 在此提出的建议旨在促进这一理解。具体来说， 将追求五个主要目标：1)作用于谷氨酸受体的新药 2)一类受体结合的动力学 将测量调节一种类型的谷氨酸反应的药物；3) 谷氨酸离开其一个受体部位的速度将是 测量；4)谷氨酸受体特性的变化-在不同的 将研究大脑的某些部分；以及，5)通过什么机制 谷氨酸反应是否可以被调节将被调查。中国政府的回应 神经元和单受体-通道复合体分子的研究 与膜片钳电生理技术相结合 一种允许快速改变细胞外溶液的灌流技术。 推广膜片钳实用的几种新方法 技术也将被利用 这项研究有助于理解突触是如何 传输发生以及其强度是如何调节的，以及 开发可以改变突触传递的药物。《知识》 Gain应该有助于深入了解 各种各样的生理过程和大脑紊乱，其中 谷氨酸受体参与其中。

The class of neurotransmitter receptor molecules activated by L-glutamate appears to mediate most fast synaptic transmission in the vertebrate central nervous system. The broad objective of the project described here is to further our pharmacological and biophysical understanding of how this important class of receptors is activated and regulated. Glutamate receptors function in nearly every category of normal central nervous system activity. There is evidence for their involvement in all sensory systems, often at multiple levels from the sensory organ to cortical association areas. The presence of glutamate responses in cerebellum, striatum, and spinal cord suggest extensive involvement in motor systems. Glutamate receptors are found at high density in the cortex and appear to be essential for higher functions such as learning and memory. A group of receptors types so deeply involved in normal brain function can also play important roles in brain dysfunction; glutamate receptors have been implicated in the etiology of many brain disorders including epilepsy, Alzheimer's disease, Huntington's disease, and schizophrenia. In addition, hypoxia induced neuronal death, as a consequence, for example, of stroke, may result from excessive activation of glutamate receptors. A description of either normal or pathological brain function will require detailed understanding, of how glutamate receptors work. The research proposed here is intended to advance that understanding. Specifically, five major goals will be pursued: 1) New drugs active at glutamate receptor sites will be characterized; 2) the kinetics of receptor binding by a class of drugs that modulate one type of glutamate response will be measured; 3) the speed with which glutamate leaves one of its receptor sites will be measured; 4) the variation in glutamate receptor properties-in different parts of the brain will be studied; and, 5) the mechanisms by which glutamate responses can be regulated will be investigated. The responses of neurons and of single receptor-channel complex molecules will be studied with the electrophysiological technique of patch clamp in combination with a perfusion technique that allows rapid extracellular solution changes. Several new approaches that generalize the utility of the patch clamp technique will also be taken advantage of This research can contribute to the understanding of how synaptic transmission takes place and how its strength is regulated, and to the development of drugs that can modify synaptic transmission. The knowledge gained should help provide insight into the mechanisms that underlie the wide variety of physiological processes and brain disorders in which glutamate receptors are involved.