ANALYSIS OF THE EXCITATORY ACTION OF ATP

细胞外三磷酸腺苷(ATP)的细胞表面受体 在体外和体内都发现了发育中的鸡骨骼肌纤维 活着。这些通道耦合到两类离子通道。这个 这项研究的目标是了解细胞和分子基础 哪些ATP激活的通道起作用，并确定其功能 这些通道在骨骼肌发育中起作用。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，也可能是发育中的胆碱能传递 神经肌肉接头。第二种可能性是ATP可能会被释放 并与其他成肌细胞上的受体相互作用 促进肌肉分化。目前拨款的具体目标是 时间段是：1)鉴定与ATP偶联的第二信使分子 受体激活一种晚期钾电流。这些实验 似乎可能导致对新的第二信使的描述，或者在 已知的第二信使影响离子的新方式的描述 通道功能。2)比较雏鸡骨骼肌对 三磷酸腺苷与哺乳动物骨骼肌和禽类平滑肌的反应 肌肉。如果对ATP的反应像在鸡骨骼肌中看到的那样 如果被发现是普遍存在的，它将极大地增加 ATP激活的通道的不同寻常的特性赋予了系统 特殊功能。3)为了检验ATP受体发挥作用的假设 在成肌细胞融合或突触形成过程中起重要作用。这些 实验将测试ATP受体可能发挥的两个最可能的作用 在发展肌肉方面发挥作用。4)确定细胞间的相互作用 调节ATP受体的表达。这些实验将允许 US确定两个受体是否在同一基因中表达 组织，三磷酸腺苷受体和乙酰胆碱受体，被调节 独立地，或以协调的方式。监管的问题 实际上中央的所有细胞都面临着 神经系统。现在可以在一个可访问的系统中研究这个问题。5) 启动研究，最终导致生化和 三磷酸腺苷受体的分子特征。 控制正常肌肉的细胞相互作用的知识 发展将为理解提供基础，也许 改善与医学有关的神经和肌肉功能缺陷。

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.