NEURAL MECHANISMS OF ANESTHESIA

麻醉的神经机制

• 批准号: 3395103
• 负责人: JOAN J KENDIG
• 金额: $ 28.35万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395103
• 关键词: Chelonia; GABA receptor; Malacostraca; adrenergic receptor; anesthetics; atmospheric pressure; axon; calcium transporting ATPase; cell membrane; conduction anesthesia; depolarizing neuromuscular blocking agent; drug interactions; drug metabolism; electron microscopy; hippocampus; hyperbaric chamber; hyperoxia; laboratory rat; membrane channels; membrane potentials; microelectrodes; neural transmission; neuromuscular junction; neuropharmacology; saltwater environment; synapses; visual cortex

Hyperbaric pressure antagonizes the anesthetic effects of anesthetic agents (pressure reversal of anesthesia). In the past, this project has used high pressure to probe the site(s) of anesthetic action in nerve cells, a strategy derived from two linked hypotheses. The first hypothesis is that pressure directly antagonizes anesthetic effects at the molecular and cellular levels; the second, that anesthesia by all agents is fundamentally a unitary phenomenon, with a single site at which all agents act. We have developed evidence against the hypothesis of direct pressure-anesthetic antagonism. Pressure reversal of anesthesia appears to be primarily indirect, and to depend on the activity- dependent synaptic processes of potentiation and facilitation. We now propose to test the unitary hypothesis of anesthesia by examining the extent to which both intravenous and inhalation anesthetic agents modify activity-dependent synaptic interactions. Intracellular studies will be continued on a simple model synapse, a crustacean neuromuscular junction, to confirm that some agents enhance the predominantly presynaptic properties of facilitation and potentiation. Field potential studies in rat hippocampal cortical slice will be carried out to conform and extend our preliminary observation of agent-specific anesthetic effects on facilitation and long-term potentiation. The majority of the proposed studies will use intracellular recording in hippocampal slice CA1 neurons to compare effects of anesthetic agents on the properties which determine the output of this cell type in response to excitatory synaptic input, emphasizing depolarization-spike initiation coupling, GABA-mediated inhibition, activity-dependent after potentials, and synaptic potentiation. In view of evidence linking anesthesia and adrenergic neurotransmission, the interaction between adrenergic agents and anesthetic effects will be examined. The results will test the extent to which a unitary hypothesis of anesthetic action can still be supported, or alternatively supply a cellular substrate for a multisite hypothesis, using a preparation form a part of mammalian brain important in arousal, waking behavior, and memory formation. The results will also provide information on the nearly explored interaction between anesthetics and activity patterns in a synaptic network. Finally, the results may account for observed differences among agents in what have been considered side effects, but which may be an integral part of their anesthetic action.

高压压力拮抗 麻醉剂（麻醉的压力逆转）。 在过去， 该项目使用高压探测 神经细胞中的麻醉作用，这是从两个 链接的假设。 第一个假设是压力直接 在分子和细胞上拮抗麻醉作用 水平；第二，所有特工的麻醉是从根本上 一个统一现象，所有代理人都具有一个单一的地点。 我们已经开发了反对直接假设的证据 压力麻醉的拮抗作用。 麻醉的压力逆转 似乎主要是间接的，并且取决于活动 - 增强和促进的依赖突触过程。 我们 现在建议通过 检查静脉和吸入的程度 麻醉剂修改活动依赖性突触相互作用。 细胞内研究将在简单的模型突触中继续进行， 甲壳类神经肌肉连接，以确认某些药物 增强促进的主要突触前特性 和增强。 大鼠海马的现场潜在研究 将进行皮质切片以符合和延长我们的 初步观察药物特异性麻醉作用对 促进和长期增强。 大多数 拟议的研究将在海马中使用细胞内记录 切片Ca1神经元比较麻醉剂对 确定此单元格的输出的属性 为了兴奋性突触输入，强调去极化尖峰 引发耦合，GABA介导的抑制作用，活性依赖性 电势之后，并突触增强。 鉴于证据 将麻醉和肾上腺素能神经传递联系起来， 肾上腺素能和麻醉作用之间的相互作用将 被检查。 结果将测试统一的程度 麻醉作用的假设仍然可以得到支持，或者 或者为多站点提供细胞底物 假设，使用制剂形成哺乳动物大脑的一部分 在唤醒，清醒行为和记忆形成中很重要。 这 结果还将提供有关几乎探索的信息 突触中麻醉和活动模式之间的相互作用 网络。 最后，结果可能解释了观察到的差异 在被认为是副作用的代理商中，但 可能是他们麻醉作用不可或缺的一部分。