Comparative mechanisms of O2 and CO2/H+ sensing in vertebrates

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Specialized cells, known as sensory receptors, allow air- and water-breathing animals to detect changes in environmental stimuli, and initiate unconscious reflex responses crucial for survival. Since oxygen (O2) is essential for animal survival, specialized O2-receptors help maintain an optimal supply of O2 to the body tissues. Thus, when environmental or blood O2 levels fall (hypoxia), e.g. at high altitude, O2-receptor cells located in specific organs are stimulated. These receptor cells respond by sending electrical signals to brain centers that trigger an increase in breathing and a redistribution of blood flow to protect vital organs (e.g. the brain). These O2-receptors can also detect high CO2 /H+ levels in blood. Our long-term goals are to understand how O2 and CO2/H+ levels are sensed, how the sensing mechanisms have evolved, how receptor organs use electrical and chemical signals for cell-cell interactions and communication with the brain, and how the organs adapt to different patterns of hypoxia. Most of our work has focused on specialized mammalian `receptor' organs, known as carotid bodies. Also, we studied extensively another organ known as the adrenal gland, which contains cells that release important `stress hormones' when animals are exposed to stressors such as hypoxia; as a result the animal becomes better adapted to cope with the stress. The basic sensing mechanisms probably arose in water-breathing animals, e.g. fish, and with NSERC funding, we were the first to show similar O2 sensing mechanisms in fish gills and mammalian carotid body. However, our recent studies suggest that information processing in the carotid body is more complex, as many different neurochemicals and additional cell-cell interactions are involved. The short-term goals of this NSERC application are partly to understand how rat carotid body cells use chemical signals to communicate with each other and with the nervous system. We will use glass electrodes to record electrical activity, fluorescent dyes to detect certain ions, pharmacological and molecular tools to determine how these chemicals act. Moreover, changes in carotid body and adrenal gland functions occur when animals (and humans) are exposed to different patterns of hypoxia. For example, long-term hypoxia (e.g. high altitude or lung/heart disease) can lead to an increase in both carotid body sensitivity and stress signals released from the adrenal gland which have beneficial effects. However, intermittent hypoxia as occurs during disordered breathing (e.g. sleep apnea) can cause over-excitation of the carotid body, leading to hypertension and heart failure. By studying how neurochemicals, receptor proteins, cell interactions, and electrical signals contribute to carotid body and adrenal gland function we expect to contribute novel information about their roles in both normal & abnormal respiratory and cardiovascular physiology.