Coordinated control of cell Ca2+ loading and triggered release from the sarcoplasmic reticulum underlies the rapid inotropic response to increased L-type Ca2+ current
Aw. Trafford et al., Coordinated control of cell Ca2+ loading and triggered release from the sarcoplasmic reticulum underlies the rapid inotropic response to increased L-type Ca2+ current, CIRCUL RES, 88(2), 2001, pp. 195-201
The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca
2+ content and systolic Ca2+ are controlled when Ca2+ entry into the cell i
s varied. Experiments were performed on voltage-clamped rat and ferret vent
ricular myocytes loaded with fluo-3 to measure intracellular Ca2+ concentra
tion ([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, w
hich is released on depolarization and (2) increasing Ca2+ entry into the c
ell. The results of this study show that the combination of these effects r
esults in rapid changes in the amplitude of the systolic Ca2+ transient. In
support of this, the changes of amplitude of the transient occur more quic
kly following changes of [Ca2+](o) than following refilling of the SR after
depletion with caffeine. We conclude that the coordinated control of incre
ased Ca2+ entry and greater fractional release of Ca2+ is an important fact
or in regulating excitation-contraction coupling.