Defining the role of cyclic nucleotide-gated cation channels in adult lung fluid homeostasis.

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In the womb, the baby?s lungs are filled with fluid. At birth, this fluid is removed so that the baby can begin to breathe. The process of removing this fluid involves the opening of tiny, specialised molecules known as channels. As the child grows to adulthood, these channels must stay open in order to prevent the lung filling up totally with fluid. If they do not, the lung begins to fill with fluid again and breathing becomes very difficult, finally resulting in serious danger. This is what often happens in: 1) diseases such as asthma, chronic bronchitis, cystic fibrosis, smoking-related illness and infections where normal liquid movement is dramatically altered and; 2) heart failure, when excess fluid collects in the lung very frequently. Although we know a lot about the channels which open at birth, we know very little about how they work in the adult lung. In fact, we are still not certain which ones are important or where exactly they are situated within the lung. We will answer these important questions using our new methods of studying these channels and their effects in small pieces of lung and in whole lung. For the first time, these studies will allow us to find out which channels are present, how they behave and which parts of the lung are most important. Why do we need to know this? This new knowledge will tell us how the adult lung normally works and will help us to understand what happens when it goes wrong. Increasing our detailed knowledge of how the lung normally deals with fluid has the potential to be applied to all the conditions mentioned above and our results will help doctors design ways of helping people to recover more quickly. This might be by the new use of medicines already available or by stimulating manufacture of new drugs which will target the mechanism discovered by our research work.