ANESHETIC MODULATION OF NATIVE NICOTINIC RECEPTORS

天然烟碱受体的麻醉调节

• 批准号: 6384938
• 负责人: PAMELA Dru FLOOD
• 金额: $ 12.63万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384938
• 关键词: Xenopus oocyte; anesthetics; catecholamines; drug screening /evaluation; electrophysiology; ganglions; general anesthesia; hemodynamics; hypothalamus; isoflurane; ketamine; mixed tissue /cell culture; motor neurons; neural transmission; neuropharmacology; neurotransmitter antagonist; neurotransmitters; nicotinic receptors; pharmacokinetics; receptor expression; sympathetic nervous system; synapses; voltage /patch clamp

The principal investigator of this mentored clinical science award is an anesthesiologist who is seeking advanced training in the physiology and pharmacology of general anesthetic action in native neurons. The long-term objectives of this proposal are two-fold. The first objective is to provide the principal investigator with the training that will allow her to become an independent medical scientist. The second objective is to understand the mechanism by which two general anesthetics cause clinically relevant changes in the sympathetic nervous system. The first objective will be obtained through mentored research and non-research activity including graduate classes in physiology and pharmacology. Training will be enhanced with weekly journal club, data review sessions departmental lecture series and interaction with colleagues. The second objective will be pursued with studies of general anesthetic activity at multiple levels of the sympathetic nervous system. General anesthetic modulation of the sympathetic nervous system allows the patient to undergo surgery without hemodynamic changes that would otherwise be detrimental. Modulation of postsynaptic sympathetic nAChRs will be studied using patch clamp recording of dispersed sympathetic ganglia neurons. General anesthetic activity at presynaptic nAChRs will be studied by monitoring the frequency of spontaneous synaptic transmission between dispersed sympathetic ganglia neurons and visceral motor neuron explants. The effects of anesthetics on excitatory input from the hypothalamus will be studied using patch clamp recording from dispersed hypothalamic neurons. The resulting information will provide understanding of the molecular mechanism underlying one of the anesthetic effects that limit anesthetic safety.

该临床科学指导奖的主要研究者是一位麻醉师，他正在寻求天然神经元全身麻醉作用生理学和药理学方面的高级培训。 该提案的长期目标有两个。 第一个目标是为主要研究者提供培训，使她能够成为一名独立的医学科学家。 第二个目标是了解两种全身麻醉药引起交感神经系统临床相关变化的机制。第一个目标将通过指导研究和非研究活动（包括生理学和药理学研究生课程）来实现。 培训将通过每周的期刊俱乐部、数据审查会议、部门讲座系列以及与同事的互动来加强。第二个目标将通过研究交感神经系统多个层面的全身麻醉活动来实现。 交感神经系统的全身麻醉调节使患者在接受手术时不会发生血流动力学变化，否则会产生不利的影响。 将使用膜片钳记录分散的交感神经节神经元来研究突触后交感神经乙酰胆碱受体的调节。 通过监测分散的交感神经节神经元和内脏运动神经元外植体之间自发突触传递的频率来研究突触前 nAChR 的全身麻醉活性。 将使用来自分散的下丘脑神经元的膜片钳记录来研究麻醉剂对下丘脑兴奋性输入的影响。 由此产生的信息将有助于了解限制麻醉安全的麻醉效应之一的分子机制。