ANESTHETIC ACTIONS AT GABA AND GLUTAMATE SYNAPSES

GABA 和谷氨酸突触的麻醉作用

• 批准号: 2701782
• 负责人: M. Bruce MacIver
• 金额: $ 21.48万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701782
• 关键词: AMPA receptors; NMDA receptors; anesthetics; central nervous system; chloride channels; electrophysiology; evoked potentials; gamma aminobutyrate; glutamates; halothane; hippocampus; inhalation anesthesia; inhibitor /antagonist; ionophores; isoflurane; laboratory rat; neurons; neuropharmacology; receptor expression; synapses; thiopental

DESCRIPTION: (Adapted from the applicant's abstract) Evidence exists for anesthetic actions at central nervous system (CNS) synapses. Some anesthetics may enhance GABA-mediated inhibitory transmission while others appear to produce CNS depression by reducing glutamate-mediated excitation. Preliminary results from these investigators suggests that several anesthetics act at both types of synapses and may summate to reduce synaptically-evoked discharge of neurons. The investigator suggests that it may be possible to develop selectively targeted anesthetics based on an understanding of actions at glutamate and GABA synapses. To do this a determination of common synaptic actions of different chemical/pharmacological classes of anesthetics is proposed. The Specific Aims are to determine: 1) the extent to which anesthetic-induced depression of CA 1 neuron discharge results from enhanced GABA-mediated transmission. 2) whether anesthetic-induced depression of glutamate-mediated synaptic responses involves enhanced GABA inhibition. 3) the cellular and molecular mechanisms of anesthetic effects at glutamate and GABA synapses. The proposed research will use the well-characterized CA 1 neuron circuit in rat hippocampus, in which GABA and glutamate mediate fast monosynaptic transmission. Evoked responses will be completely blocked by selective GABA and glutamate receptor antagonists. Electrophysiological recordings will be combined with selective NMDA and AMPA receptor anatagonists to investigate anesthetic-induced depression of glutamate-mediated excitatory postsynaptic potentials. Parallel studies will determine the extent to which an anesthetic-induced depression of CA 1 neuron discharge can be reversed by blocking GABA receptor/Cl- channels.

描述：（根据申请人的摘要改编）存在证据 中枢神经系统（CNS）突触的麻醉作用。 一些 麻醉药可以增强GABA介导的抑制性传播，而其他 通过减少谷氨酸介导的激发，似乎会产生CNS抑郁症。 这些研究者的初步结果表明，有几个 两种类型的突触中的麻醉药作用，可能会汇总以减少 神经元的突触诱发排放。 调查人员建议 可能有可能基于一个 了解谷氨酸和GABA突触的作用。 这样做 确定不同的共同突触行动 提出了麻醉药的化学/药理类别。 具体 目的是确定：1​​）麻醉诱导的抑郁症的程度 Ca 1神经元排出的结果是GABA介导的透射率增强。 2）麻醉诱导的谷氨酸介导的突触 响应涉及增强的GABA抑制作用。 3）细胞和分子 谷氨酸和GABA突触上麻醉作用的机制。 这 拟议的研究将在大鼠中使用良好的CA 1神经元电路 海马，其中GABA和谷氨酸介导快速单突触 传播。 诱发的响应将被选择性GABA完全阻止 和谷氨酸受体拮抗剂。 电生理记录将是 结合选择性NMDA和AMPA受体Anatongonists进行研究 麻醉诱导的谷氨酸介导的兴奋性突触的抑郁症 潜力。 并行研究将确定 麻醉诱导的Ca 1神经元排出的抑郁症可以逆转 阻止GABA受体/Cl-通道。