Dominant role of mitochondria in protection against a delayed neuronal Ca2+ overload induced by endogenous excitatory amino acids following a glutamate pulse

被引:48
作者
Khodorov, B [1 ]
Pinelis, V [1 ]
Storozhevykh, T [1 ]
Vergun, O [1 ]
Vinskaya, N [1 ]
机构
[1] RUSSIAN ACAD MED SCI,INST PEDIAT,MOSCOW,RUSSIA
关键词
mitochondrial Ca2+ uptake; Ca2+ overload; endogenous excitatory amino acid; cultured neuron;
D O I
10.1016/0014-5793(96)00873-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca2+ loads induced by glutamate or 25 mM K+ pulses. The mitochondrial Ca2+ uptake was suppressed by application of 0.5 mu M antimycin A or 3-5 mM NaCN in combination with 2.5 mu g/ml oligomycin. In most cells such treatments both in the presence and in the absence of external Na+ failed to abolish the early fast phase of [Ca2+](i) recovery following a 1-min 100 mu M glutamate pulse, However, the late slow phase of [Ca2+](i) recovery in the presence of mitochondrial poisons was transformed into a delayed [Ca2+](i) elevation culminating in the neuronal Ca2+ overload. Suppression of the Na+/Ca2+ exchange caused by glutamate-induced [Na+]i elevation promoted the development of delayed Ca2+ increase. Under identical conditions, the high [Ca2+](i) transient induced by 25 mM K+ was never accompanied by a delayed Ca2+ elevation. The glutamate-induced delayed Ca2+ increase could be readily abolished by the removal of external Ca2+ or by application in the post-glutamate period of the antagonist of NMDA receptors, 100-200 mu M AP-5. The results obtained suggest that mitochondria play a dominant role in the protection against the neuronal Ca2+ overload induced by endogenous excitatory amino acids released in response to a short-term glutamate challenge.
引用
收藏
页码:135 / 138
页数:4
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