R. Zucchi et al., POSTISCHEMIC CHANGES IN CARDIAC SARCOPLASMIC-RETICULUM CA2- A POSSIBLE MECHANISM OF ISCHEMIC PRECONDITIONING( CHANNELS ), Circulation research, 76(6), 1995, pp. 1049-1056
We investigated the modifications of cardiac ryanodine receptors/sarco
plasmic reticulum Ca2+ release channels occurring in ischemic precondi
tioning. In an isolated rat heart model, the injury produced by 30 min
utes of global ischemia was reduced by preexposure to three 3-minute p
eriods of global ischemia (preconditioning ischemia). The protection w
as still present 120 minutes after preconditioning ischemia but disapp
eared after 240 minutes. Three 1-minute periods of global ischemia did
not provide any protection. In the crude homogenate obtained from ven
tricular myocardium, the density of [H-3]ryanodine binding sites avera
ged 372+/-18 fmol/mg of protein in the control condition, decreased 5
minutes after preconditioning ischemia (290+/-15 fmol/mg, P<.01), was
still significantly reduced after 120 minutes (298+/-17 fmol/mg,, P<.0
5), and recovered after 240 minutes (341+/-21 fmol/mg). Three 1-minute
periods of ischemia did not produce any change in ryanodine binding.
The K-d for ryanodine (1.5+/-0.3 nmol/L) was unchanged in all cases. I
n parallel experiments, the crude homogenate or a microsomal fraction
was passively loaded with Ca-45, and Ca2+-induced Ca2+ release was stu
died by the quick filtration technique. In both preparations, the rate
constant of Ca2+-induced Ca2+ release decreased 5 and 120 minutes aft
er preconditioning ischemia (homogenate values: 19.7+/-1.4 and 18.9+/-
0.9 s(-1) vs a control value of 25.4+/-1.7 s(-1) P<.05 in both cases)
and recovered after 240 minutes (23.0+/-1.9 s(-1)). The Ca2+ dependenc
e of Ca2+-induced Ca2+ release was not affected by preconditioning isc
hemia. In conclusion, changes in sarcoplasmic reticulum Ca2+-release c
hannels occur after brief ischemia and reperfusion, are closely correl
ated with the development of myocardial protection Versus sustained is
chemia, and might play a role in the pathogenesis of ischemic precondi
tioning.