Modulation of CICR has no maintained effect on systolic Ca2+: simultaneousmeasurements of sarcoplasmic reticulum and sarcolemmal Ca2+ fluxes in rat ventricular myocytes
Aw. Trafford et al., Modulation of CICR has no maintained effect on systolic Ca2+: simultaneousmeasurements of sarcoplasmic reticulum and sarcolemmal Ca2+ fluxes in rat ventricular myocytes, J PHYSL LON, 522(2), 2000, pp. 259-270
1. The effects of modulating Ca2+-induced Ca2+ release (CICR) in single car
diac myocytes were investigated using low concentrations of caffeine (< 500
mu M) in reduced external Ca2+ (0.5 mM). Caffeine produced a transient pot
entiation of systolic [Ca2+](i) (to 800 % of control) which decayed back to
control levels.
2. Caffeine decreased the steady-state sarcoplasmic reticulum (SR) Ca2+ con
tent. As the concentration of caffeine was increased, both the potentiation
of the systolic Ca2+ transient and the decrease in SR Ca2+ content were in
creased. At higher concentrations, the potentiating effect decayed more rap
idly but the rate of recovery on removal of caffeine was unaffected.
3. A simple model in which caffeine produces a fixed increase in the fracti
on of SR Ca2+ which is released could account qualitatively but not quantit
atively for the above results.
4. The changes in total [Ca2+] during systole were obtained using measureme
nts of the intracellular Ca2+ buffering power. Caffeine initially increased
the fractional release of SR Ca2+ This was followed by a decrease to a lev
el greater than that under control conditions. The fraction of systolic Ca2
+ which was pumped out of the cell increased abruptly upon caffeine applica
tion but then recovered back to control levels. The increase in fractional
loss is due to the fact that, as the cytoplasmic buffers become saturated,
a given increase in systolic total [Ca2+] produces a larger increase in fre
e [Ca2+] and thence of Ca2+ efflux.
5. These results confirm that modulation of the ryanodine receptor has no m
aintained effect on systolic Ca2+ and show the interdependence of SR Ca2+ c
ontent, cytoplasmic Ca2+ buffering and sarcolemmal Ca2+ fluxes. Such analys
is is important for understanding the cellular basis of inotropic intervent
ions in cardiac muscle.