The genetically determined cardiomyopathy of the Syrian hamster is being studied as a model of spontaneously developing cardiomyopathies. Using an integrated approach to the problem of cardiomyopathic development in comparison with normal, we are focusing on defects in cellular handling of calcium. We have identified disease-related alterations in the sarcolemma, mitochondria and the sarcoplasmic reticulum. Studies are proposed here to better characterize the calcium regulation of the heart cell in both the normal and disease states. The binding and transport of calcium by the sarcolemma and the relationship of calcium transport changes to the alterations in the cardiac electrophysiology will be investigated. Our previous studies of mitochondrial calcium transport and binding will be extended to better define regulation of mitochondrial calcium handling. Disease-related differences in sarcoplasmic reticular calcium transport and accumulation will be examined. The mechanisms underlying the reportedly ameliorative effects of chronic Verapamil or taurine administration on cardiomyopathic hamsters will be investigated.