Na+/Ca2+ exchange during Ca2+ repletion is not a prerequisite for the Ca2+ paradox in isolated rat hearts.
Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. Since previously a Ca2+ paradox without prior increase of total intracellular [Na+] ([Na+]i) has been observed, we investigated whether local accumulation of Na+ close to the inner side of the sarcolemma during 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 perfusion (37°C) in isolated rat hearts (group I). Subsequently, hearts were perfused with a standard, Na+- and Ca2+-containing solution. Verapamil was used to prevent contracture due to the absence of Na+/Ca2+ exchange during Na+-free perfusion in the presence of Ca2+. In group II, the Ca2+-free period was omitted, and in group III normal extracellular [Na+] was used throughout. 23Na-NMR was used to monitor intra- 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 and 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 III [Na+]i was 10.9±2.2 mM during control perfusion and did not change significantly after 10 min Ca2+-free perfusion. It is concluded that accumulation of Na+ close to the inner side of the sarcolemma during Ca2+ depletion is not a prerequisite for the Ca2+ paradox.
Department of Cardiology, Heart Lung Institute, University Hospital, P.O. Box 85500, NL-3508 GA Utrecht, The Netherlands.
M A
MA
Jansen
C J
CJ
Van Echteld
T J
TJ
Ruigrok
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D012975:Sodium Isotopes / Q000378:metabolism
D012975:Sodium Isotopes; D012964:Sodium; D002118:Calcium