NEUROTRANSMITTER RELEASE USING LIPOSOMES

这项拟议研究的总体目标是加深我们对 钙依赖神经递质的细胞和膜方面 放手。脂质体将被用来向神经末梢输送物质， 已知或怀疑具有生理活性，这是困难的或 由于没有这样的传递系统，不可能进行其他研究。 改善试剂对神经组织的靶向性有朝一日可能被证明 对某些神经科疾病的治疗方法的开发很有用 疾病。这项提议将利用我们两家公司的综合专长 电生理学实验室(青蛙运动神经的突触前功能 和膜学(脂质体的开发和应用)。它 旨在回答以下问题：1)最佳方案是什么 脂质体包封物向马达输送的条件 神经末梢？2)脂质体传递神经末梢的机制是什么？ 内容物到运动神经末梢？作为推论，什么是 与参与神经的功能有关的意义 膜，与脂膜的相互作用？3)是钙离子进入 是诱发ACh释放还是促进ACh释放所必需的？4) 细胞对钙、锶和钡的选择性是该过程所固有的 诱发ACh释放，还是反映了钙从储藏中的置换 网站？这个问题对于巴来说尤其重要，因为它 用于膜片钳研究。5)是第二信使系统(例如， 三磷酸肌醇、钙调蛋白、突触素I)参与调控 神经递质释放？

The overall objective of the proposed research is to further our knowledge of the cellular and membrane aspects of calcium-dependent neurotransmitter release. Liposomes will be used to deliver to nerve terminals substances, known or suspected to be physiologically active, which are difficult or impossible to study otherwise because of absence of such a delivery system. Improving the targeting of reagents to neural tissue could someday prove useful for the development of treatments for some classes of neurological diseases. The proposal will exploit the combined expertise of our laboratories, electrophysiology (presynaptic function at frog motor nerve endings) and membranology (development and applications of liposomes). It is designed to answer the following questions: 1) What are the optimal conditions for delivering the encapsulated contents of liposomes to motor nerve endings? 2) What is the mechanism by which liposomes deliver their contents to motor nerve terminals? As a corollary, what is the significance, with respect to the function of the participating nerve membrane, of its interaction with the liposomal membrane? 3) Is Ca entry required for evoked ACh release or for facilitation of ACh release? 4) Is the cellular selectivity for Ca, Sr and Ba intrinsic to the process of evoked ACh release or does it reflect the displacement of Ca from storage sites? This question is particularly important with respect to Ba, which is used in patch clamp studies. 5) Are second messenger systems (e.g., inositol tris phosphate, calmodulin, synapsin I) involved in modulation of neurotransmitter release?