Coordinated control of cell Ca2+ loading and triggered release from the sarcoplasmic reticulum underlies the rapid inotropic response to increased L-type Ca2+ current

Abstract

The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca2+ content and systolic Ca2+ are controlled when Ca2+ entry into the cell is varied. Experiments were performed on voltage-clamped rat and ferret ventricular myocytes loaded with fluo-3 to measure intracellular Ca2+ concentration ([Ca2+]i). Increasing external Ca2+ concentration ([Ca2+]o) from 1 to 2 mmol/L increased the amplitude of the systolic Ca2+ transient with no effect on SR Ca2+ content. This constancy of SR content is shown to result because the larger Ca2+ transient activates a larger Ca2+ efflux from the cell that balances the increased influx. Decreasing [Ca2+]o to 0.2 mmol/L decreased systolic Ca2+ but produced a small increase of SR Ca2+ content. This increase of SR Ca2+ content is due to a decreased release of Ca2+ from the SR resulting in decreased loss of Ca2+ from the cell. An increase of [Ca2+]o has two effects: (1) increasing the fraction of SR Ca2+ content, which is released on depolarization and (2) increasing Ca2+ entry into the cell. The results of this study show that the combination of these effects results in rapid changes in the amplitude of the systolic Ca2+ transient. In support of this, the changes of amplitude of the transient occur more quickly following changes of [Ca2+]o than following refilling of the SR after depletion with caffeine. We conclude that the coordinated control of increased Ca2+ entry and greater fractional release of Ca2+ is an important factor in regulating excitation-contraction coupling.