Role of calcium in glutamate-mediated toxicity: mechanisms of calcium fluxes in rabbit hippocampus in vivo investigated with microdialysis
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Calcium ions are known to play a key role in the mechanism of excitotoxic and ischemic neuronal injury.< Hippocampal CA1 neurons> are selectively susceptible to this kind of damage. Although various <calcium ionophores>have been identified in the hippocampal neurons, it is not clear what the main pathway for Ca?+ entry is during overexcitation. These studies were aimed to estimate a potential contribution of different types of calcium ionophores in calcium redistribution to hippocampal neurons in vivo.The local microdialysis technique, combined with the 45Ca?+ utilizing method was used to measure the changes in extracellular Ca?+ concentrations ([Ca?+]e) in the rabbit hippocampus in vivo, and to apply active substances directly to the hippocampus. The application of N-methyl-D-aspartate (NMDA) resulted in a large, dose-dependent decrease of [Ca?+]e, which was sensitive to APV and MK-801, but was only slightly reduced by <nimodipine> and <amiloride>. The effect of high potassium medium was less pronounced and only slightly inhibited by nimodipine. However it was inhibited by 75% in the presence of MK-801 and then completely cancelled by nimodipine. To visualize the depolarization-induced calcium influx to hippocampal cells, KC1-induced cellular swelling and resulting shrinkage of the extracellular space, monitored with [U-14C]sucrose , was taken into account in calculating these data. These results indicate that calcium redistribution into hippocampal neurons through NMDA channels may highly exceed calcium fluxes in the hippocampus, attributable to a stimulation of the L-type voltage-sensitive calcium channels.
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