Signal Transduction in Intrapulmonary Chemoreceptors

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DESCRIPTION (provided by applicant): We will study the cellular mechanisms of CO2 transduction in avian intrapulmonary chemoreceptors (IPC) as a model for general principles of respiratory CO2 transduction in vertebrates. We will use this research to introduce undergraduate and graduate students at Northern Arizona University to biomedical research using hands-on lab experiences and training in scientific practice. Aim I of this proposal will test whether active proton transport by v-type H+ ATPase and H+/K+-ATPase participate in pH regulation and CO2 transduction in IPC. Concanomycin A and esomeprazole will be used while recording single unit chemoreceptor responses to phasic CO2 stimuli. Aim II will test whether transient lactic acid accumulation or KATP channels play roles in IPC spike frequency adaptation (SFA), using lactate infusion and glibenclamide with single-unit recordings. Aim III will test the hypothesis that IPC share some signal transduction properties found in mammalian CO2-sensitive pulmonary stretch receptors (PSR), which would indicate a degree of phylogenetic homology between PSR and IPC. 4-amino pyridine, a fast K+ ion channel blocker shown to decrease PSR response to CO2, and gadolinium chloride, a blocker of stretch activated ion channels which impairs PSR response to lung inflation, will be studied in single-unit IPC. Aim IV will investigate the role of Na+/K+ ATPase in energizing the IPC membrane and influencing Ca++ levels via Na+/Ca++ exchange. This research will enhance understanding of respiratory chemoreceptors in general, attract and train of future scientists at NAU, and may suggest medical treatments useful for treating disorders in CO2 chemosensitivity. PUBLIC HEALTH RELEVANCE: This research investigates fundamental neural processes that detect CO2 levels in the body and send neural signals to the brain that control breathing. This is important for human health, because better understanding of respiratory CO2 chemotransduction may help develop more effective treatments and drugs for the loss of CO2 chemosensitivity, a common complication seen in patients with severe cardiopulmonary disease. The research will also be used to stimulate interest and give hands-on scientific experience to undergraduate and graduate students at Northern Arizona University interested in biomedical research careers.