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Involvement of Na + –Ca 2+ Exchanger in Reperfusion‐induced Delayed Cell Death of Cultured Rat Astrocytes
Author(s) -
Matsuda Toshio,
Takuma Kazuhiro,
Nishiguchi Emi,
Asano Shoichi,
Hashimoto Hitoshi,
Azuma Junichi,
Baba Akemichi
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01582.x
Subject(s) - sodium calcium exchanger , amiloride , sodium–hydrogen antiporter , chemistry , extracellular , ouabain , nifedipine , intracellular , calcium , programmed cell death , microbiology and biotechnology , biophysics , sodium , biochemistry , biology , apoptosis , organic chemistry
In some cells, Ca 2+ depletion induces an increase in intracellular Ca 2+ ([Ca 2+ ] i ) after reperfusion with Ca 2+ ‐containing solution, but the mechanism for the reperfusion injury is not fully elucidated. Using an antisense strategy we studied the role of the Na + ‐Ca 2+ exchanger in reperfusion injury in cultured rat astrocytes. When astrocytes were perfused in Ca 2+ ‐free medium for 15–60 min, a persistent increase in [Ca 2+ ] i was observed immediately after reperfusion with Ca 2+ ‐containing medium, and the number of surviving cells decreased 3–5 days latter. The increase in [Ca 2+ ] i was enhanced by low extracellular Na + ([Na + ] o ) during reperfusion and blocked by the inhibitors of the Na + ‐Ca 2+ exchanger amiloride and 3,4‐dichlorobenzamil, but not by the Ca 2+ channel antagonists nifedipine, Cd 2+ and Ni 2+ . Treatment of astrocytes with antisense, but not sense, oligodeoxynucleotide to the Na + ‐Ca 2+ exchanger decreased Na + –Ca 2+ exchanger protein level and exchange activity. The antisense oligomer attenuated reperfusion‐induced increase in [Ca 2+ ] i and cell toxicity. The Na + ‐Ca 2+ exchange inhibitors 3,4‐dichlorobenzamil and ascorbic acid protected astrocytes from reperfusion injury partially, while the stimulators sodium nitroprusside and 8‐bromo‐cyclic GMP and low [Na + ] o exacerbated the injury. Pretreatment of astrocytes with ouabain and monensin caused similar delayed glial cell death. These findings suggest that Ca 2+ entry via the Na + –Ca 2+ exchanger plays an important role in reperfusion‐induced delayed glial cell death.