ANALYSIS OF THE EXCITATORY ACTION OF ATP

ATP 兴奋作用的分析

• 批准号: 3411227
• 负责人: RICHARD IRWIN HUME
• 金额: $ 10.36万
• 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/3411227
• 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 突触小泡，但在大多数突触中它的功能尚不清楚。 最近发现，鸡骨骼肌纤维是 被三磷酸腺苷兴奋(Kolb和Wakelam，1983；Hume和Honig，1986) 为研究ATP的作用提供了极好的机会 在突触，因为神经肌肉连接是目前为止最好的 具有突触的特征，无论是在成熟阶段还是在发育过程中。 肌肉细胞以突触为特征，无论是在成熟期还是在成熟期 发展。培养中的肌肉细胞非常容易获得 电生理和生化研究，所以这些 观察也为细胞的详细研究开辟了道路 以及ATP介导的兴奋的分子基础。具体的 该项目的目标是： 1.解决关于 作为ATP基础的单通道引起了去极化。 2.确定是否涉及第二信使系统 在三磷酸腺苷引起的去极化。 3.考察长期的时间进程和机制 这种反应表现出的脱敏。 4.为了检验受体激活涉及一种 胞外磷酸化。 5.确定ATP受体在其中发挥的任何功能作用 神经肌肉传递或肌肉发育。 这些实验旨在进一步了解 肌肉前体细胞和幼体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发挥作用，或者在 神经肌肉连接的形成。关于蜂窝网络的知识 控制正常发展的交互作用将提供一个 在医学上理解的基础，也许是改善的基础 神经和肌肉功能的相关缺陷。