ENERGY-DEPENDENT TRANSPORT OF CALCIUM TO THE EXTRACELLULAR-SPACE DURING ACUTE-ISCHEMIA OF THE RAT-HEART

Citation
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
Citations number
53
Categorie Soggetti
Cardiac & Cardiovascular System","Cell Biology
ISSN journal
00222828
Volume
30
Issue
8
Year of publication
1998
Pages
1631 - 1642
Database
ISI
SICI code
0022-2828(1998)30:8<1631:ETOCTT>2.0.ZU;2-3
Abstract
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