ANESHETIC MODULATION OF NATIVE NICOTINIC RECEPTORS

天然烟碱受体的麻醉调节

基本信息

批准号：
6635756
负责人：
PAMELA Dru FLOOD
金额：
$ 12.77万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2005-04-30
项目状态：
已结题

项目摘要

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.

该指导临床科学奖的主要研究者是一名麻醉师，他正在寻求本地神经元中全身麻醉作用的生理学和药理学的高级培训。该提议的长期目标是两个方面。第一个目的是向主要研究人员提供培训，使她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在交感神经系统中引起临床相关的变化的机制。第一个目标将通过指导的研究和非研究活动获得，包括生理学和药理学研究生班。通过每周期刊俱乐部，数据审查会议部门的演讲系列以及与同事的互动，将增强培训。第二个目标将通过对交感神经系统多个层次的一般麻醉活性的研究来追求。交感神经系统的一般麻醉调节允许患者进行手术而无需进行血液动力学变化，否则这会是有害的。将使用分散的交感神经神经元记录贴片夹记录突触后交感神经NACHR的调节。通过监测分散的交感神经神经元和内脏运动神经元外植体之间自发的突触传播的频率，可以研究突触前NACHR的一般麻醉活性。麻醉药对下丘脑兴奋性输入的影响将使用分散下丘脑神经元的斑块夹记录进行研究。最终的信息将提供对限制麻醉安全性的麻醉作用之一的分子机制的理解。