PRESYNAPTIC MECHANISMS OF NEUROTRANSMITTER RELEASE

神经递质释放的突触前机制

• 批准号: 3440991
• 负责人: CLARK A LINDGREN
• 金额: $ 5.79万
• 依托单位: ALLEGHENY COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3440991
• 关键词: acetylcholine; adenosine; adenosine triphosphate; adenylate kinase; antibody; autoimmune disorder; calcium flux; electrical potential; electrophysiology; facial muscles; fluorescent dye /probe; lizards; myasthenia gravis; nerve endings; neuromuscular junction; neurotransmitter metabolism; synapses

The research described in this proposal focuses on the cellular mechanisms involved in the release of neurotransmitter at a chemical synapse. Since calcium ions are essential to neurotransmitter release, a major theme of the research is the regulation of intracellular calcium by the nerve terminal under various physiological and pathological conditions. Given the central importance of synaptic transmission both to the normal functioning of the nervous system and to pathological disturbances of this function, it is essential that this process be understood in detail. The experiments outlined in this proposal will be performed on the nerve-muscle synapse in the ceratomandibularis muscle of the lizard, Anolis carolinensis. This muscle is very thin and flat, and the presynaptic nerve endings contain large boutons. Using focal extracellular recording, four separate currents -- including a voltage-dependent calcium current -- can be measured in the presynaptic terminal. This allows measurements of transmitter release, made by conventional intracellular recording, to be directly compared to the presynaptic currents responsible for eliciting the release of neurotransmitter. With such information, it will be possible to directly address several issues related to the initiation and regulation of neurotransmitter release from a vertebrate nerve terminal. Specifically, the work described in this proposal is organized around three questions which have been formulated to exploit the inherent optical advantages of the ceratomandibularis muscle and the unique opportunity to monitor changes in calcium current and neurotransmitter release from the same nerve terminal. (1) How do ATP and/or adenosine modulate neurotransmitter release at the vertebrate neuromuscular junction? (2) What is the cellular basis of the defect in neuromuscular transmission that develops in humans with Lambert-Eaton myasthenic syndrome (LEMS)? (3) What is the precise spatial and temporal distribution of calcium in an active presynaptic nerve terminal?

该提案中描述的研究重点是细胞机制 参与化学突触中神经递质的释放。 自从 钙离子对于神经递质释放至关重要，这是一个主要主题 该研究是通过神经调节细胞内钙 在各种生理和病理条件下的末端。 给出 突触传播的核心重要性既可以正常 神经系统的功能以及对此的病理障碍 功能，必须详细理解此过程至关重要。 该提案中概述的实验将在 蜥蜴的ceratomandibularis肌肉中的神经肌肉突触 carolinensis。 这种肌肉非常薄又平坦，突触前神经 结尾包含大型装饰。 使用局灶性细胞外记录，四个 单独的电流 - 包括电压依赖性钙电流 - 可以 在突触前末端进行测量。 这允许测量 传统细胞内记录制造的发射器释放，为 直接与负责引发的突触前电流进行比较 神经递质的释放。 有了这样的信息 直接解决与启动和法规有关的几个问题 神经递质从脊椎动物神经末端释放。 具体而言，该提案中描述的工作大约是三个 已经制定了用于利用固有光学的问题 Ceratomandibularis肌肉的优势和独特的机会 监测钙电流的变化和神经递质从 相同的神经末端。 （1）ATP和/或腺苷调节如何 神经递质在脊椎动物神经肌肉连接处的释放？ （2）什么 是神经肌肉传播缺陷的细胞基础 与兰伯特·伊顿肌无力综合征（LEMS）一起在人类中发展？ （3）什么 是钙在活动中的精确空间和时间分布 突触前神经终末？