ANALYSIS OF THE EXCITATORY ACTION OF ATP

ATP 兴奋作用的分析

• 批准号: 3411230
• 负责人: RICHARD IRWIN HUME
• 金额: $ 7.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411230
• 关键词: adenosine triphosphate; cell membrane; chick embryo; depolarizing neuromuscular blocking agent; growth /development; membrane potentials; muscle stimulant; myofibrils; neuromuscular transmission; phosphorylation; second messengers; synapses

Adenosine Triphosphate (ATP) is present in many types of synaptic vesicles, but at most synapses it has not known function. The recent discovery that chick skeletal muscles fibers are excited by ATP (Kolb and Wakelam, 1983; Hume and Honig, 1986) provides an excellent opportunity for examining the role of ATP at synapses, since the neuromuscular junction is by far the best characterized synapse, both in maturity and during development. Muscle cells characterized synapse, both in maturity and during development. Muscle cells in culture are very accessible for electrophysiological and biochemical studies, so these observations also open the way for detailed studies of the cellular and molecular basis of ATP mediated excitation. The specific aims of this project are: 1. To resolve conflicting results regarding the nature of the single channels that underlie the ATP evoked depolarization. 2. To determine whether a second messenger system is involved in the ATP evoked depolarization. 3. To examine the time course and mechanism of the long term desensitization that this response displays. 4. To test the hypothesis that receptor activation involves an extracellular phosphorylation. 5. To determine any functional role that ATP receptors play in neuromuscular transmission or in muscle development. These experiments are designed to further understanding of the function of a receptor found on muscle precursor cells and young muscle cells. The early appearance of this receptor suggests that it may play a role in the development of muscle cells or in the formation of neuromuscular junctions. Knowledge of the cellular interactions that control normal development would provide a basis for understanding, and perhaps ameliorating, medically relevant deficits in nerve and muscle function.

三磷酸腺苷（ATP）存在于许多类型的 突触囊泡，但在大多数突触，它已不知道的功能。 最近发现鸡骨骼肌纤维 ATP兴奋（Kolb和Wakelam，1983; Hume和Honig，1986） 为研究ATP的作用提供了一个极好的机会， 在突触处，因为神经肌肉接头是迄今为止最好的 在成熟期和发育期都具有突触的特征。 在成熟期和发育期， 发展 培养中的肌肉细胞很容易被 电生理学和生物化学研究，所以这些 这些观察也为详细研究细胞内的 和ATP介导兴奋的分子基础。 具体 该项目的目标是： 1. 为了解决关于 ATP诱发去极化的单通道。 2. 以确定是否涉及第二信使系统 ATP诱发的去极化。 3. 研究长期的时间进程和机制 这种反应表现出的脱敏作用。 4. 为了验证受体激活涉及 细胞外磷酸化 5. 为了确定ATP受体在 神经肌肉传递或肌肉发育。 这些实验旨在进一步了解 在肌肉前体细胞和年轻人身上发现的受体的功能 肌肉细胞 这种受体的早期出现表明， 它可能在肌肉细胞的发育中起作用， 神经肌肉接头的形成。 细胞的知识 控制正常发育的相互作用将提供 理解的基础，也许改善，医学， 神经和肌肉功能的相关缺陷。