Role of calcium in glutamate-mediated toxicity: mechanisms of calcium fluxes in rabbit hippocampus in vivo investigated with microdialysis.
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 Ca2+ 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 45Ca2+ utilizing method was used to measure the changes in extracellular Ca2+ concentrations ([Ca2+]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 [Ca2+]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, KCl-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.
Lazarewicz
J W
JW
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw.
Salińska
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003956:Dialysis; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D011817:Rabbits
D005971:Glutamates; D018698:Glutamic Acid; D002118:Calcium