Article,

Ca$^2+$ scraps: local depletions of free Ca$^2+$ in cardiac sarcoplasmic reticulum during contractions leave substantial Ca$^2+$ reserve.

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Circ. Res., 93 (1): 40--45 (July 2003)
DOI: 10.1161/01.RES.0000079967.11815.19

Abstract

Free Ca$^2+$ inside the sarcoplasmic reticulum (Ca$^2+$SR) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, Ca$^2+$SR regulates cardiac contractility. We directly measure Ca$^2+$SR in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic Ca$^2+$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$^2+$SR at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca$^2+$ release shows that the inherently positive feedback of Ca$^2+$-induced Ca$^2+$ 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$^2+$ store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure.

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