Ca. Schumacher et al., ENERGY-DEPENDENT TRANSPORT OF CALCIUM TO THE EXTRACELLULAR-SPACE DURING ACUTE-ISCHEMIA OF THE RAT-HEART, Journal of Molecular and Cellular Cardiology, 30(8), 1998, pp. 1631-1642
Objective: Acute ischemia is associated with rapidly decreasing contra
ctility and Ca2+-transients. Diastolic intracellular Ca2+, however, on
ly mildly increases until development of contracture. The purpose of t
his study was to investigate whether changes of cellular calcium handl
ing during the early phase of ischemia are associated with active sarc
olemmal calcium transport. Methods: Changes of extracellular concentra
tion of calcium ([Ca2+](o)) and tetramethylammonium ([TMA(+)](o)), to
estimate extracellular space, were simultaneously measured with ion-sp
ecific electrodes in the globally ischemic rat heart. The magnitude an
d direction of sarcolemmal calcium transport were calculated from [Ca-
2](o) corrected for changed extracellular water content. Energy depend
ence of sarcolemmal calcium transport was investigated by application
of iodoaceticacid (IAA) to inhibit anaerobic glycolysis, and the invol
vement of the sarcoplasmic reticulum (SR) was studied by application o
f thapsigargin. The effect of anoxia and thapsigargin on cytosolic and
SR calcium was studied in isolated myocytes with the fluorescent indi
cator indo-1. Results: [Ca2+](o) increased and extracellular space gra
dually decreased in the ischemic intact heart, During the first 7 min,
the increase of [Ca2+](o) was associated with net outward transport o
f calcium. Subsequently, net re-uptake occurred. IAA completely abolis
hed outward transport and influx was accelerated and enhanced. Applica
tion of thapsigargin attenuated outward transport. In electrically-sti
mulated myocytes, anoxia caused little change of diastolic calcium and
depletion of SR. Thapsigargin reduced both calcium transient amplitud
e and SR calcium without affecting diastolic calcium. During three suc
cessive short episodes of ischemia/reperfusion (preconditioning), outw
ard transport of calcium progressively decreased. Conclusion: During t
he early phase of global ischemia, energy dependent transport of calci
um to the extracellular space occurs. At least part of this calcium or
iginates from SR. During the later stage of ischemia, re-uptake of cal
cium occurs. which is associated with development of contracture. (C)
1998 Academic Press