Ca 2 Scraps Local

Free [Ca ] inside the sarcoplasmic reticulum ([Ca ]SR) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, [Ca ]SR regulates cardiac contractility. We directly measure [Ca ]SR in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic [Ca ]SR (1 to 1.5 mmol/L) is only partially depleted (24% to 63%) during contraction. There is little temporal delay in the decline in [Ca ]SR at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca release shows that the inherently positive feedback of Ca -induced Ca release terminates, despite a large residual driving force. These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure. (Circ Res. 2003;93:40-45.)