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

Abstract

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 (ICa), 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 ICa increases as the SR Ca2+ content is augmented. Regulation of SR Ca2+ content is thus a means by which cardiac contractility is regulated.