Grant: Operating Grant

In the neck region near major arteries, 'receptor' cells in tiny organs help maintain blood chemicals at particular levels via the control of breathing. These 'receptor' cells sense blood oxygen, carbon dioxide, and acidity, and send electrical signals to the brain that help correct any major disturbances. Abnormalities in this reflex pathway can have fatal consequences. For example, changes in 'receptor' cell properties are associated with clinical conditions such as obstructive lung disease (COPD), sleep apnea (where breathing stops periodically), hypertension, and congestive heart failure. These conditions are associated with fluctuations in blood oxygen levels, which can lead to hyper-activity in the reflex pathway, compromising blood pressure regulation and heart function. Our investigations aim to understand how these 'receptor' cells work, how they communicate with the brain, and how their properties change in disease states. To simplify the system, in one approach we isolate these 'receptor' cells from rats and grow them in tissue culture dishes alone, or with the nerve cells that contact them in the animal. Recent studies have shown that these rat 'receptor' cells behave similarly to those in humans. We grow the cells in an incubator under different oxygen levels, thereby mimicking the environment experienced in disease conditions. Also, we can expose live animals (rats) to environments where oxygen levels can be varied in precise patterns, so as to mimic the above clinical conditions. We can then apply various techniques (e.g. recording of electrical activity, imaging, molecular biology) to help understand how the 'receptor' cells communicate with nerve cells, and how their properties change in different oxygen environments. This understanding will help in the design of new drugs to target and correct abnormalities that arise in the aforementioned clinical conditions.