ANESTHETICS, ISCHEMIA, AND CNS CALCIUM CHANNELS

麻醉剂、缺血和中枢神经系统钙通道

• 批准号: 2188666
• 负责人: THOMAS Joseph John BLANCK
• 金额: $ 13.72万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2188666
• 关键词: anesthetics; brain cell; calcium channel; calcium channel blockers; calcium flux; calcium indicator; calcium metabolism; central nervous system; cerebral ischemia /hypoxia; chemical binding; electrophysiology; halothane; homeostasis; isoflurane; laboratory rat; lipid bilayer membrane; membrane reconstitution /synthesis; molecular site; neurons; radiotracer; synaptosomes; tissue /cell culture; voltage gated channel

The long term objectives of this proposal are to determine whether voltage dependent Ca2+ channels (VDCC) are a major site of action of the volatile anesthetics, halothane and isoflurane, and whether isoflurane can attenuate the ischemic changes that have been observed in VDCC. The more limited aims are to define the effects of halothane and isoflurane on the binding properties of Ca2+ channel antagonists to VDCC, and on the movement of Ca2+ through single Ca2+ channels and populations of Ca2+ channels. Ca2+ homeostasis and the activity of VDCC have also been implicated in the pathophysiology of ischemic CNS damage, and preliminary data suggest that isoflurane might ameliorate CNS damage by an action on VDCC. This proposal will examine the interaction of isoflurane, VDCC, and ischemia to determine whether changes in channel density and Ca2+ flux occur and can be attenuated by isoflurane. Radioligand binding assays, Ca2+ flux measurements with fura 2 in isolated synaptosomes and cultured neurons, and with electrophysiologic measurements of single Ca2+ channels in reconstituted membranes will be performed to achieve the specific aims. The potential therapeutic advantage of isoflurane and related compounds in preventing or lessening ischemic damage would be addressed in subsequent proposals if findings derived from the described studies suggest a rational therapeutic approach.

该提案的长期目标是确定电压是否 依赖的Ca2+通道（VDCC）是挥发性的主要作用部位 麻醉药，氟烷和异氟烷，以及异氟烷是否可以 减弱在VDCC中观察到的缺血变化。更多 有限的目的是定义卤代和异氟烷对 Ca2+通道拮抗剂与VDCC的结合特性，并在 CA2+通过CA2+的单个CA2+通道和种群的运动 频道。 CA2+稳态和VDCC的活动也 涉及缺血性中枢神经系统损害的病理生理学和初步 数据表明，异氟烷可能会通过对 VDCC。该建议将研究异氟烷，VDCC和 缺血以确定通道密度的变化和Ca2+通量的变化 发生并可以通过异氟烷减弱。放射性结合测定法， Ca2+通量测量在孤立的突触体中用Fura 2和培养的 神经元，以及单个Ca2+通道的电生理测量 将在重构的膜中执行以实现特定目的。 异氟烷和相关化合物的潜在治疗优势 随后将解决或减少缺血性损害 建议如果从所描述的研究得出的发现表明A 理性的治疗方法。