beta-Adrenoceptor stimulation decreases the calcium-sensitivity of cardiac contractile proteins through cAMP-dependent phosphorylation of troponin I and others. Agents such as alpha 1-adrenergic receptor agonists, endothelin, angiotensin II et al. that stimulate PI turnover elicit positive inotropic responses associated with increase in the calcium-sensitivity. Phorbol ester decreases the apparent sensitivity of the contractile proteins to calcium ion through the phosphorylation of troponin T and others. Myocardial contractile force may be altered by increasing or decreasing the calcium responsiveness of the myofilaments by various drugs, which change the calcium affinity of calcium-binding proteins such as troponin C and calmodulin. Moreover, we isolated a new calcium-binding protein (S100C) from porcine heart and cloned the cDNA for this protein. Modulation of intracellular calcium signaling in cardiac muscle by protein phosphorylation and drugs awaits further investigation.