Ionized calcium is the most important cell regulator of cardiac muscle. Intracellular ionized calcium (10 to the minus 5th power to 10 to the minus 7th power M) is readily exchangeable with the extracellular fraction of serum ionized calcium (approximately 10 to the minus 3rd power M). Serum ionized calcium (Ca 2 ion) can be directly measured by ion specific electrode. The level of Ca 2 ion can be raised by infusing calcium salts or reduced by infusing complexing agents such as Na3 citrate. We propose to explore situations in which alterations in Ca 2 ion may contribute to the pathogenesis of cardiac and skeletal muscle disease. These include cardiomyopathies of various types and rhabdomuolysis. We also propose to investigate the potential therapeutic potential of short-term increases or decreases in Ca 2 ion, such as Na3 citrate infusion in hypercalcemia and calcium-dopamine infusions for post-operative inotropic support in cardiac surgery patients. A final area of exploration is the cellular mechanism of action of calcium antagonists, which appear to act by combining with a specific calcium receptor. Characteristics of this receptor will be further investigated by direct binding studies with high specific activity radioligands, and an attempt will be made to elucidate why these drugs act selectively on coronary vascular tissue.