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 依赖性 Ca2+ 通道 (VDCC) 是挥发性物质的主要作用位点 麻醉剂、氟烷和异氟烷，以及异氟烷是否可以 减轻 VDCC 中观察到的缺血性变化。越多 有限的目标是确定氟烷和异氟烷对 Ca2+通道拮抗剂与VDCC的结合特性，以及 Ca2+ 通过单一 Ca2+ 通道和 Ca2+ 群体的运动 渠道。 Ca2+ 稳态和 VDCC 的活性也已被 与缺血性中枢神经系统损伤的病理生理学有关，初步研究 数据表明，异氟醚可能通过作用来改善中枢神经系统损伤 VDCC。该提案将研究异氟烷、VDCC 和 缺血以确定通道密度和 Ca2+ 通量是否发生变化 发生并可被异氟烷减弱。放射性配体结合测定， 使用 fura 2 测量分离和培养的突触体中的 Ca2+ 通量 神经元，以及单个 Ca2+ 通道的电生理测量 将在重组膜中进行以实现特定目标。 异氟烷和相关化合物的潜在治疗优势 预防或减轻缺血性损伤将在随后的研究中得到解决 如果所描述的研究得出的结果表明 合理的治疗方法。