PHYSIOLOGY & STRUCTURE OF THE ACHR CHANNEL & ENDPLATE

生理

• 批准号: 3402156
• 负责人: John A. Dani
• 金额: $ 13.05万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402156
• 关键词: Anura; acetylcholine; calcium channel blockers; calcium transporting ATPase; conformation; electrophysiology; fresh water environment; laboratory rat; membrane channels; membrane model; membrane permeability; membrane potentials; membrane proteins; membrane transport proteins; microelectrodes; microinjections; neuromuscular junction; nicotinic receptors; phosphorylation; point mutation; protein sequence; protein structure function; receptor sensitivity; site directed mutagenesis; synapses; tissue /cell culture

The purpose of the proposed research is to study the function and structure of the nicotinic acetylcholine receptor (AChR) and then to describe the results cohesively in terms of the amino acid sequences of the receptor subunits. A better understanding of single AChRs will then serve as a background for exploring the AChR's involvement in complex processes at the neuromuscular junction. Electrophysiological techniques, theoretical approaches, fluorescent ion indicators, and biophysical studies of structure will provide a body of information to guide site-directed mutagenesis experiments with the AChR. The mutation studies allow direct comparison of structure and function to test existing hypotheses and to generate better ones. Calcium's permeability, interactions with other permeants, and influence on protein phosphorylation will be examined as a possible unique self-regulating mechanism of AChRs at the neuromusclar junction. Quantifying and determining the biological importance of calcium entry through AChRs is not only important at cholinergic synapses; it also could suggest regulatory roles of calcium that enters the cell through other synaptic receptors not known primarily as Ca channels. The proposed research directly relates the structure and function of the AChR to its overall roles at the neuromuscular endplate. In addition, the studies will contribute to the general understanding of possible mechanisms involved in regulating synapses.

拟议研究的目的是研究功能和 烟碱乙酰胆碱受体（ACHR）的结构，然后 用氨基酸凝聚的结果 受体亚基的序列。 更好地理解 然后，单个ACHR将作为探索的背景 ACHR参与神经肌肉的复杂过程 交界处。 电生理技术，理论方法， 荧光离子指标和结构的生物物理研究 将提供一系列信息来指导现场定向 ACHR的诱变实验。 突变研究 直接比较结构和功能以测试现有 假设并产生更好的假设。 钙的渗透性，与其他渗透性的相互作用，以及 对蛋白质磷酸化的影响将被检查为 ACHR的独特自我调节机制可能 Neuromusclar Junction。 量化和确定 通过ACHRS进入钙的生物学重要性不仅是 对胆碱能突触很重要；它也可能建议调节 通过其他突触进入细胞的钙的作用 受体主要不称为CA通道。 拟议的研究直接关联了结构和功能 ACHR在神经肌肉端板上的总体作用。 此外，研究将有助于一般 了解调节所涉及的可能机制 突触。