THE PHYSIOLOGY OFPRESYNAPTIC NERVE TERMINALS

突触前神经末梢的生理学

• 批准号: 3396694
• 负责人: MORDECAI P BLAUSTEIN
• 金额: $ 21.93万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-08-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396694
• 关键词: Cirripedia; acetylcholine; adenosine triphosphate; adenosinetriphosphatase; anesthetics; barbiturates; calcium metabolism; calcium transporting ATPase; catecholamines; cell membrane; cell osmotic pressure; cyclic AMP; electron microscopy; electrophysiology; endoplasmic reticulum; gamma aminobutyrate; ganglionic blocking agents; hydrogen transport; ion transport; laboratory rat; magnesium; membrane model; membrane potentials; molecular psychobiology; muscle cells; neural transmission; neurochemistry; neurotransmitters; norepinephrine; organelles; potassium channel; radiotracer; sodium potassium exchanging ATPase; synapses; synaptosomes

The aim of this project is to elucidate the physiological and pharmacological properties of mammalian presynaptic nerve terminals. Pinched-off terminals (synaptosomes) from rat brain are used for these studies. In one type of study, tracer 45Ca flux methods and fluorometric methods (with a Ca-sensitive fluorochromic indicator) will be employed to determine how the smooth endoplasmic reticulum (SER), mitochondria and the plasma membrane interact to help regulate the cytoplasmic free Ca2+ concentration, and to determine how these organelles respond to the changes in free Ca2+ that occur with neuronal activity. The resulting data should enable us to model these interrelationships accurately. In the second type of study, which comprises the major portion of the proposed program, the physiological, pharmacological and biochemical properties of the various potassium channels that are present in nerve terminals will be characterized. Tracer (86Rb) efflux studies will be used to determine the sensitivities of the K channels to various drugs and toxins; the channels will be incorporated into planar lipid bilayers to study the kinetic and pharmacologic properties of single K channels; the binding characteristics of K channel blockers and modulators will be investigated in synaptic membranes; the pharmacological properties will then be used to help identify the K channel proteins that will be isolated, characterized, and reconstituted into lipid bilayers to verify their functional integrity. The first K channel that will be investigated in this way is the non-inactivating, voltage-regulated K channel. This channel has been identified as the high-affinity phencyclidine (PCP) receptor (about 95,000 and 80,000 Dalton MW) in the brain. The results may help to explain how PCP induces a schizophrenia-like syndrome. We will then use similar methods to investigate the properties of a K channel that is activated by certain opiates.

该项目的目的是阐明生理和 哺乳动物突触前神经末端的药理特性。 从大鼠脑中使用的夹紧终端（突触体）用于这些 研究。 在一种类型的研究中，示踪剂45CA通量方法和荧光测定法 方法（带有CA敏感的荧光指标）将用于 确定光滑的内质网（SER），线粒体和如何 质膜相互作用以帮助调节细胞质游离Ca2+ 集中度，并确定这些细胞器如何应对变化 在神经元活性发生的游离Ca2+中。 结果数据应 使我们能够准确地对这些相互关系进行建模。 在第二类 研究的研究包括拟议计划的主要部分 各种生理，药理和生化特性 神经末端中存在的钾通道将是 特征。 示踪剂（86RB）外排研究将用于确定 K通道对各种药物和毒素的敏感性；频道 将纳入平面脂质双层，以研究动力学和 单K通道的药理特性；结合特征 K频道阻滞剂和调节器将在突触中进行研究 膜；然后，药理特性将用于帮助 识别将隔离，表征的K通道蛋白，并且 重构为脂质双层以验证其功能完整性。 以这种方式进行调查的第一个K渠道是 无活化的电压调节的K通道。 这个频道已经 被识别为高亲和力的苯克林（PCP）受体（约95,000 和80,000个大脑中的道尔顿MW）。 结果可能有助于解释如何 PCP诱导精神分裂症样综合征。 然后我们将使用类似的 研究被激活的K通道的性质的方法 某些鸦片。