Ion channel changes in intermittent hypoxia

间歇性缺氧时离子通道的变化

• 批准号: 6564828
• 负责人: DIANA L KUNZE
• 金额: $ 26.7万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564828
• 关键词: afferent nerve; blood pressure; carotid body; chemoreceptors; electrophysiology; hypoxia; immunocytochemistry; laboratory rat; neural information processing; neurophysiology; neuroregulation; pulmonary respiration; respiration regulatory center; respiratory hypoxia; solitary tract nucleus; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): The ultimate goal of this project is to uncover the alterations in voltage-gated ion channel expression distribution and/or function that occur as a consequence of chronic intermittent hypoxia (CIH) and to show how these changes contribute to the long term effects of CIH on respiratory control and arterial pressure. The immediate focus of this study is on the first two sets of neurons in the chemoreflex pathway, the chemoreceptor sensory afferent neurons and the relay neurons in the nucleus of the solitary tract (nTS) with which they synapse. The study will focus on CIH-induced changes in each of the two sets of neurons and will employ a combination of electrophysiological, immunocytochemical, molecular and modeling techniques. These experiments are designed to distinguish activity-dependent changes initiated at the glomus cells from direct effects of intermittent hypoxia on the neurons. In the second phase of the study the consequences of the ion channel modifications will be examined in the transmission of activity across the sensory/relay neuron synapse in the nTS brain slice preparation. In the third phase of our studies, we will delve further into the mechanisms that underlie the CIH-induced plasticity in the ion channels as we utilize information obtained in conjunction with the other projects in the program that address mechanisms of gene regulation in CIH. It is anticipated that these studies will provide insight to the machinery that underlies neural-mediated increases in arterial pressure and respiratory responses that accompany CIH.

描述（由申请人提供）： 该项目的最终目标是揭示电压门控的变化 离子通道表达式分布和/或功能作为一个 慢性间歇性缺氧（CIH）的结果，并显示这些 变化有助于CIH对呼吸控制和 动脉压。这项研究的直接重点是前两套 化学反射途径中的神经元，化学感受器感觉传递 神经元和孤立道（NTS）核中的继电器神经元与 他们突触。该研究将重点介绍CIH诱导的每一个变化 两组神经元将采用电生理学的组合 免疫细胞化学，分子和建模技术。这些实验是 旨在区分glomus启动的活动依赖性变化 间歇性缺氧对神经元直接影响的细胞。在 研究的第二阶段是离子通道修饰的后果 将在跨感觉/继电器的活动传播中检查 NTS脑切片制剂中的神经元突触。在我们的第三阶段 研究，我们将进一步研究CIH诱导的基础的机制 当我们利用以下信息时，离子通道中的可塑性 与该计划中的其他项目的结合，以解决 CIH中的基因调节。预计这些研究将提供 对基于动脉增加神经介导的增加的机械的洞察力 CIH伴随的压力和呼吸反应。