Amount of calcium in the sarcoplasmic reticulum: Influence on excitation-contraction coupling in heart muscle

Real-time imaging of the concentration of intracellular calcium ([Ca²⁺](i)) has been carried out in heart cells using confocal imaging and patch-clamp techniques. Here we review recent investigations that used genetically engineered mice that lack phospholamban (PL knockout) to investigate the mechanisms of excitation-contraction (EC) coupling in heart. The heart cells from PL knockout (KO) mice exhibit [Ca²⁺](i) transients that are larger than normal. Similarly, the elementary units of EC coupling, called Ca²⁺ sparks, were found to be more frequent in PL KO heart cells than normal heart cells. This finding is consistent with the findings that cell-wide [Ca²⁺](i) transients arise as Ca²⁺ sparks sum during the EC coupling process. Finally, it was determined that the amount of Ca²⁺ within the sarcoplasmic reticulum (SR) was greater in the PL KO cardiac myocytes than in controls. Analysis of the results indicate that the larger [Ca²⁺](i) transients and the more frequent Ca²⁺ sparks are due to the greater amount of Ca²⁺ within the SR of PL KO myocytes, as the Ca²⁺ current (I(Ca)), which triggers the Ca²⁺ sparks and the [Ca²⁺](i) transient, was the same in control and PL KO heart cells. We conclude that the amount of Ca²⁺ released from the SR per unit of triggering I(Ca) increases as the SR Ca²⁺ content is augmented. Regulation of SR Ca²⁺ content is thus a means by which cardiac contractility is regulated.