COMPARTMENTALISATION OF CAMP SIGNALLING IN NORMAL AND HYPERTROPHIC CARDIOMYOCYTES

Familial Hypertrophic Cardiomyopathy (FHC) is an hereditary disease, transmitted as an autosomal dominant trait and the major cause of sudden death in young adults. Its frequency, in the general population, has been estimated to be close to 0.2%. The disease is characterised by thickening of the heart walls, which leads to an impairment of cardiac function. The aim of the proposed research is to study some aspects of the cardiac cells physiology that may be involved in the pathogenesis of FHC. Although some of the DNA mutations responsible for FHC have been identified, the mechanisms that lead from the mutation to the hypertrophy of the heart are not known. The current hypothesis is that the disease may result from the misbehaviour of some of the molecules involved in the transduction of signals inside the cells. The role of these molecules is to control that the cell reacts in the proper way to a specific external stimulus. One of such molecules is cAMP. In this study I will employ a new methodology, that I recently developed, with which it is possible to monitor the fluctuations of cAMP in live cells. This method relies on the use of two fluorescent molecules of different colours that can be introduced in live cells and observed at the microscope. Changes in cAMP appear as chenges in fluorescence intensity. With this technique it is possible to study the role of cAMP with a resolution (both in space and time) that was not possible before and its application may yield information useful for developing new and effective therapies.