Ion channel changes in intermittent hypoxia

描述（由申请人提供）： 这个项目的最终目标是揭示电压门控的改变， 离子通道表达分布和/或功能， 慢性间歇性缺氧（CIH）的后果，并显示这些 这些变化有助于CIH对呼吸控制的长期影响， 动脉压本研究的直接重点是前两组 神经元的化学感受器反射途径，化学感受器感觉传入 孤束核（nTS）中的神经元和中继神经元， 它们与之形成突触。这项研究将集中在CIH引起的变化， 这两组神经元，并将采用电生理学， 免疫细胞化学、分子和建模技术。这些实验 旨在区分血管球起始的活性依赖性变化 间歇性缺氧对神经元的直接影响。在 研究的第二阶段是离子通道修饰的后果 将在通过感觉/中继的活动传输中进行检查 nTS脑切片制备中的神经元突触。在我们的第三阶段 研究，我们将进一步深入研究CIH诱导的机制， 离子通道的可塑性，因为我们利用在 与方案中的其他项目结合，解决 CIH的基因调控预计这些研究将提供 深入了解神经介导的动脉粥样硬化增加的机制 压力和呼吸反应伴随CIH。

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.