The main sensors of arterial oxygen (02) tension are the carotid bodies (CB). Although they are critically important during infancy, they are not fully developed at birth, and take time to mature. The site of O2 sensing is believed to be the type I cell, which depolarizes in response to hypoxia, leading to Ca2+ influx through calcium channels, a rise in intracellular calcium and release of neurotransmitters which are thought to stimulate carotid sinus nerve endings. We previously reported that the type I cell calcium response to hypoxia matures after birth, and our recent studies suggest that several aspects of this cascade change after birth, as follows: (a) depolarization of type I cells by hypoxia is minimal in cells from newborns and increases with age; (b)the O2-sensitivity of a background K+ conductance is small in cells from newborns and increases with age; and (c) calcium currents of immature, but not mature, type cells are inhibited 50% by hypoxia. The proposed work will test the hypothesis that developmental changes in the O2-sensitivity of a background """"""""leak"""""""" K+ conductance account, in part, for postnatal maturation of carotid chemoreceptor O2 sensitivity. In addition, we will determine whether (1) background K+ conductance is carried by one major background K+ channel type, the O2 sensitivity of which increases with age; or (2) background K+ conductance in type I cells is carried by at least 2 channel types, one O2-sensitive and one non-O2-sensitive, and development involves a change in the ratio of the O2-sensitive to non-O2-sensitive channels. We will also seek to understand whether developmental shifts occur in 0a-sensitive calcium channels during maturation. The results will answer important questions about the mechanisms underlying postnatal development of carotid chemoreceptor function. The ultimate goal of the proposed studies is to understand how the carotid chemoreceptors mature and how development is modulated, so that a number of potentially life threatening disorders such as asthma, bronchopulmonary dysplasia, apnea and sudden infant death syndrome (SIDS) can be better treated or prevented.
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