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Control of Intracellular Calcium in Arrhythmias

Ziel

Ventricular arrhythmias are a major cause of mortality. Currently there is no effective treatment available, largely because our understanding of their molecular basis is poor. Altered intracellular Ca handling may be a final common pathway predisposing to ventricular tachycardias and sudden death in acquired or congenital heart diseases. In particular, dysfunction of the SR Ca release channel (ryanodine receptor, RyR2) has been implicated in arrhythmogenesis and sudden death in heart failure and in catecholaminergic polymorphic ventricular tachycardia (CPVT), a fatal inherited arrhythmogenic disease characterised by mutations in RyR2. Understanding the complex function of the RyR2 Ca channel and its regulatory mechanisms, therefore, holds the promise to develop new diagnostic and therapeutic strategies for effective treatment of these lethal arrhythmias. The CONTICA investigators are a multidisciplinary team composed of cardiologists, molecular biologists, biophysicists and physiologists with established and complementary interests & expertise in the study of intracellular Ca handling and arrhythmias.
The goal pursued by the CONTICA group is the elucidation of the molecular mechanisms linking defective RyR2 funcion to the generation of arrhythmias. Employing a wide range of state-of-the-art techniques, the group will perform in depth studies on RyR dysfunction in animal and human arrhythmias on the molecular, cellular and whole organism level. Of particular importance, data gathered from the world's largest collective of individuals affected by mutations in RyR2 will reveal novel insights into the genetics of CPVT and enable genotype-phenotype correlations and expression studies of mutated RyR2 in cell lines & animals. The combined knowledge gained from these studies will be used to develop and test novel diagnostic approaches and antiarrhythmic drugs to help alleviate one of the largest health burdens to the European society, ie malignant ventricul...

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FP6-2004-LIFESCIHEALTH-5
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MEDIZINISCHE UNIVERSITAET GRAZ
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