ANALYSIS OF THE EXCITATORY ACTION OF ATP

ATP 兴奋作用的分析

• 批准号: 3411228
• 负责人: RICHARD IRWIN HUME
• 金额: $ 12.74万
• 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 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411228
• 关键词: adenosine triphosphate; cell cell interaction; cell membrane; chick embryo; cholinergic receptors; membrane channels; membrane potentials; muscle stimulant; myogenesis; neuromuscular transmission; potassium channel; receptor; receptor coupling; second messengers; striated muscles; synaptogenesis

Cell surface receptors for extracellular adenosine triphosphate (ATP) are found on developing chick skeletal muscle fibers, both in vitro and in vivo. These channels are coupled to two classes of ion channels. The goals of this study are to understand the cellular and molecular basis by which ATP activated channels operate, and to determine the function of these channels in developing skeletal muscle. Since ATP is present in cholinergic vesicles at high concentration, one possibility is that there may be purinergic, as well as cholinergic transmission at developing neuromuscular junctions. A second possibility is that ATP may be released from some myoblasts, and interact with receptors on other myoblasts to promote muscle differentiation. The specific aims for the current grant period are: 1) To identify the second messenger molecule that couples ATP receptors to the activation of a late potassium current. These experiments seem likely to result in the description of a new second messenger, or in the description of novel way that a known second messenger can affect ion channel function. 2) To compare the response of chick skeletal muscle to ATP with the responses of mammalian skeletal muscle and avian smooth muscle. If responses to ATP like those seen in chick skeletal muscle are found to be widespread, it will greatly increase the likelihood that the unusual properties of the ATP-activated channels endows the system with a special function. 3) To test the hypotheses that ATP receptors play an essential role in myoblast fusion or during synaptogenesis. These experiments will test the two most likely roles that ATP receptors might play in developing muscle. 4) To determine how cell-cell interactions regulate the expression of the ATP receptors. These experiments will allow us to determine whether two receptors that are expressed in the same tissue, ATP receptors and acetylcholine receptors, are regulated independently, or in a coordinated manner. The problem of the regulation of multiple receptors is faced by virtually all cells of the central nervous system. The issue can now be studied in an accessible system. 5) To initiate studies that will ultimately lead to the biochemical and molecular characterization of the ATP receptor. Knowledge of the cellular interactions that control normal muscle development will provide a basis for understanding, and perhaps ameliorating, medically relevant deficits in nerve and muscle function.

细胞外三磷酸腺苷（ATP）的细胞表面受体是 在发育中的鸡骨骼肌纤维上发现，无论是在体外还是在体外， vivo. 这些通道耦合到两类离子通道。 的 本研究的目的是通过以下方式了解细胞和分子基础： ATP激活通道的运作，并确定功能 这些通道在骨骼肌发育中的作用。 由于ATP存在于 高浓度的胆碱能囊泡，一种可能性是， 可能是嘌呤能，以及胆碱能传输在发展中国家 神经肌肉接头 第二种可能性是ATP可能被释放 来自一些成肌细胞，并与其他成肌细胞上的受体相互作用， 促进肌肉分化。 目前赠款的具体目标 阶段是：1）确定耦合ATP的第二信使分子 受体激活晚期钾电流。 这些实验 似乎可能导致描述一个新的第二信使，或 已知第二信使可以影响离子的新方式的描述 通道功能 2)比较鸡骨骼肌对 ATP与哺乳动物骨骼肌和鸟类平滑肌的反应 肌肉. 如果像鸡骨骼肌那样对ATP的反应， 如果发现它是普遍的，它将大大增加的可能性， ATP激活通道的不寻常特性赋予了系统 特殊功能 3)为了验证ATP受体在细胞内起作用的假设， 在成肌细胞融合或突触发生过程中起重要作用。 这些 实验将测试ATP受体可能发挥的两种最有可能的作用， 在发展肌肉方面发挥作用。 4)为了确定细胞间的相互作用 调节ATP受体的表达。 这些实验将使 我们来确定是否两个受体表达在同一个 组织，ATP受体和乙酰胆碱受体，受到调节 独立地或以协调的方式。 监管的问题 事实上，中枢神经系统的所有细胞都面临着多种受体的共同作用。 神经系统 现在可以在一个无障碍系统中研究这个问题。 第五章） 启动研究，最终将导致生物化学和 ATP受体的分子特征。 了解控制正常肌肉的细胞相互作用 发展将为理解提供基础，也许 改善神经和肌肉功能的医学相关缺陷。