PRESYNAPTIC MECHANISMS OF NEUROTRANSMITTER RELEASE

本提案中描述的研究集中在细胞机制上。 参与化学突触中神经递质的释放。自.以来 钙离子对神经递质的释放是必不可少的，这是 这项研究是通过神经调节细胞内钙离子 在各种生理和病理条件下终末期。vt.给出 突触传递对正常人群的核心重要性 神经系统的功能及其病理性紊乱 功能，因此必须详细了解这一过程。 本提案中概述的实验将在 蜥蜴颈上颌肌中的神经-肌肉突触 卡罗琳。这块肌肉很薄很平，突触前神经 结尾包含较大的回合。使用焦点细胞外记录，四个 单独的电流--包括电压相关的钙电流--可以 在突触前终末被测量。这允许测量 传送器释放，通过传统的细胞内记录进行， 直接与突触前电流相比 神经递质的释放。有了这样的信息，就有可能 直接解决与发起和监管有关的几个问题 脊椎动物神经末梢释放的神经递质。 具体地说，本提案中描述的工作围绕三个方面组织 提出的问题是为了利用固有的光学 颈上颌下肌的优势和独特的机会 监测钙电流和神经递质释放的变化 同样的神经末梢。(1)三磷酸腺苷和/或腺苷如何调节 脊椎动物神经肌肉接头的神经递质释放？(2)什么？ 是神经肌肉传递缺陷的细胞基础 在患有Lambert-Eaton肌无力综合征(LEMS)的人类中发生？(3)什么 是钙在体内的精确时空分布 突触前神经末梢？

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?