Ion channel changes in intermittent hypoxia

描述(由申请人提供)： 这个项目的最终目标是发现电压门控的变化 离子通道表达分布和/或功能 慢性间歇性低氧(CIH)的后果以及这些 变化有助于CIH对呼吸控制和 动脉压。这项研究的直接焦点是前两组 化学感受器感觉传入的化学反射通路中的神经元 孤束核(NTS)中的神经元和中继神经元 它们会进行突触。这项研究将集中在CIH引起的每一种 这两组神经元将采用电生理、 免疫细胞化学、分子和建模技术。这些实验是 旨在区分从球体开始的依赖活动的变化 间歇性低氧对神经细胞的直接影响。在 第二阶段研究离子通道改变的后果 将在感官/中继器的活动传递中被检测 NTS脑片制备中的神经元突触。在我们的第三阶段 研究后，我们将进一步深入研究CIH诱导的 离子通道的可塑性，因为我们利用在 与计划中涉及以下机制的其他项目相结合 脑出血中的基因调控。预计这些研究将提供 洞察神经介导的动脉血压升高背后的机制 伴随CIH的压力和呼吸反应。

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.