NA+ CA2+ EXCHANGE DURING CA2+ REPLETION IS NOT A PREREQUISITE FOR THECA2+ PARADOX IN ISOLATED RAT HEARTS/

Ca2+ paradox damage has been suggested to be determined by Na+ entry d uring Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletio n. Since previously a Ca2+ paradox without prior increase of total int racellular [Na+] ([Na+](i)) has been observed, we investigated whether local accumulation of Na+ close to the inner side of the sarcolemma d uring Ca2+ depletion plays a role in the Ca2+ paradox by replacing all extracellular Na+ by Li- 5 min before and during 10 min Ca2+-free per fusion (37 degrees C) in isolated rat hearts (group I). Subsequently, hearts were perfused with a standard, Na+- and Ca2+-containing solutio n. Verapamil was used to prevent contracture due to the absence of Na/Ca2+ exchange during Na+-free perfusion in the presence of Ca2+. In g roup II, the Ca2+-free period was omitted, and in group III normal ext racellular [Na+] was used throughout. Na-23-NMR was used to monitor in tra- and extracellular Na+ signals. Total creatine kinase release was 2,977+/-413, 36+/-24 and 3170+/-297 IU/g dry weight in groups I, II an d III respectively, indicating a full Ca2+ paradox in groups I and III . [Na+](i) decreased from 11.3+/-0.6 mM during control perfusion to 1. 2+/-0.4 mM after 10 min Ca2+ depletion in group I, whereas in group II I [Na+](i) was 10.9+/-2.2 mM during control perfusion and did not chan ge significantly after 10 min Ca2+-free perfusion. It is concluded tha t accumulation of Na+ close to the inner side of the sarcolemma during Ca2+ depletion is not a prerequisite for the Ca2+ paradox.