The major scientific objective of the CONTICA project is to determine the subcellular mechanisms underlying fatal inherited arrhythmias related to mutations in the SR Ca²⁺ release channel (ryanodine receptor, RyR2). Based on initial evidence that arrhythmias observed in patients with heart failure (acquired arrhythmias) are also caused by defective intracellular Ca²⁺ handling and RyR2 dysfunction, we will compare the basic mechanisms of inherited arrhythmias in transgenic animals harbouring RyR2 mutations to those of acquired arrhythmias in animal models of hypertrophy and heart failure, as well as in native human myocardium. In addition, mathematical modelling will aid in understanding mechanisms of arrhythmias as well as in predicting susceptibility to triggered arrhythmias. The ultimate goal of the CONTICA investigators is to develop novel diagnostic and therapeutic concepts and test new pharmacological compounds that may be effective in preventing inherited and acquired arrhythmias related to abnormalities in intracellular Ca²⁺ handling.