The cardiac relaxing system (CRS: sarcoplasmic reticulum) represents at least one of the potential pools of calcium available for the activation or contraction. We propose to study calcium accumulation and release from the sarcoplasmic reticulum and factors which control them, i.e. the relation of calcium release to calcium binding and factors which control them independently The proposed areas of study will include: 1) further characterization of the normal kinetics of calcium accumulation and release and investigation of those factors which influence independently the two described calcium binding sites; 2) utilization of stopped flow spectrophotometry for the analysis of early events in the calcium binding cycle and their relationship to calcium ATPase; 3) the use of pathologic and pharmacologic interventions and specific inhibitors to further delineate the nonsteady state kinetics of calcium binding and release; 4) investigation of the recently describedinteractions between the glycogenolytic system, the phosphorylating enzymes, protein kinase and phosphorylase b kinase, and sarcoplasmic reticulum calcium metabolism. This latter evaluation will also be useful in the investigation of the mode of action of ionotropic drugs and possibly the mode of action of various pathologic interventions.