Ion channel changes in intermittent hypoxia

Case Western Reserve University, Cleveland OH

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Abstract

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.