MATURATION OF THE HYPOXIC VENTILATORY RESPONSE

Oregon Health And Science University, Portland OR

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Adapted from the Investigator's Abstract): The proposed experiments are designed to test the hypothesis that the lack of hypoxic respiratory depression in mice at P1-P3 results from gamma-aminobutyric acid (GABA), acting at GABAA receptors, depolarizing the resting membrane potential and thereby exciting respiratory neurons at this stage of development. Experiments are proposed in decerebrate and vagotomized mice to show that the greater respiratory drive in P1-P3 mice compared to P7-P10 pups is central in origin. Pharmacologic and genetic techniques will be used to determine the role of GABA in hypoxic hyperpnea and depression during early postnatal development in unanesthetized mice. Whole cell recordings will also be performed in brainstem slices to determine membrane potential and the reversal potential for chloride in the presence of a GABAa agonist. Changes in the chloride potential may underlie disturbances in respiratory drive and apnea in premature human newborns.