PROTECTION OF ISOLATED RAT-HEART AGAINST THE CA2+ PARADOX - ARE GAP JUNCTION CHANNELS INVOLVED

被引:4
作者
DIEDERICHS, F
机构
[1] Institute of Clinical Biochemistry, Hannover Medical School
关键词
CA2+ PARADOX; HYPOTHERMIA; ACIDOSIS; POLYETHYLENE GLYCOL; HEPTANOL; INTRACELLULAR CA2+; INTRACELLULAR NA+; INTRACELLULAR PH; CA2+ DEPLETION;
D O I
10.1016/S0022-2828(05)82392-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Enzyme release from isolated Langendorff-perfused rat hearts was studied under various protective conditions against the Ca2+ paradox. In addition sarcosolic free cation concentrations and the membrane potential were measured employing ion-selective microelectrode techniques during Ca2+-free perfusion. Low temperature (18 degrees C), low pH (6.5 or 6.1), and polyethylene glycol (9%) during Ca2+-free perfusion all protected isolated hearts against the Ca2+ paradox. Protection could only be afforded if the protective agent was continuously present from the beginning of the Ca2+-free perfusion period. A 10 min ''normal'' Ca2+-free pre-perfusion was sufficient to abolish the protective potency of the subsequent perfusion phase in the presence of the protective agent. The gap junction channel blocker heptanol (2 mmol/l) markedly decreased enzyme release during re-perfusion, but did not afford protection. Sarcosolic free cation concentrations were measured during Ca2+-free acidic perfusion. [Na+](i) was markedly increased to about 44 mmol/l without predisposing to cell damage under these conditions. A marked reduction of cell damage was also afforded under conditions of hypoxia during Ca2+- and substrate-free perfusion. Acidosis (pH(e) = 6.5) under these conditions prevented a lethal increase of [Ca2+](i) (2 mu mol/l) and partially preserved a negative membrane potential. It is concluded that the predisposition to the Ca2+ paradox is produced by a permeabilisation of gap junction channels at low [Ca2+](e) and that upon re-elevation of [Ca2+](e) a serious Ca2+ influx proceeds through these leaks.
引用
收藏
页码:1301 / 1309
页数:9
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