Comparative study of oxygen sensing in adult and developing vertebrates

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The control of oxygen uptake is important to all vertebrates for survival and adaptation to new environments.  Specialized cells, called oxygen chemoreceptors, detect changes in blood or environmental oxygen and initiate a cascade of events that ultimately lead to adaptive, physiological changes in respiratory rate and cardiovascular function.  While many studies have addressed these issues using mammalian models, many questions and controversies still surround the cellular mechanisms of oxygen chemoreception, and these processes are poorly defined in aquatic vertebrates.  This Discovery Grant application proposes research to fill these voids and: (i) identify the physiological role(s) of chemoreceptor membrane ion channels in converting a low-oxygen stimulus into a meaningful cellular signal, (ii) characterize the chemical and functional basis of communication between oxygen-sensitive chemoreceptors and sensory neurons, and (iii) study the development of these processes from embryo to adult.  The proposed experiments will be performed on aquatic vertebrates that bear gills, e.g. zebrafish, goldfish, and amphibian larvae.  Experimental techniques will include sensitive patch-clamp recording of isolated chemoreceptors and sensory neurons to detect changes in electrical current through membrane ion channels, and high-resolution confocal microscopy.  It is anticipated that this research will provide the first description of the cellular and neurochemical basis of oxygen sensing, and the development of these processes, in aquatic vertebrates.  This research will also provide a greater understanding of how respiratory regulation may have evolved.  These findings will constitute significant advances in the fields of oxygen sensing, neurobiology and comparative physiology.  The proposed program will support the training of an average of 3 graduate students per year at the M.Sc. or Ph.D. level.