Excitotoxic amino acids cause appearance of magnetic resonance spectroscopy-observable zinc in superfused cortical slices.
(1) The effects of glutamate and NMDA on the free intracellular calcium concentration ([Ca2+]i) have been followed in superfused cortical slices using the 19F-magnetic resonance indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA). (2) Glutamate (0.5 or 1 mM) caused a 75-100% increase in [Ca2+]i, and a new resonance was attributed to zinc-5FBAPTA, which was confirmed from its disappearance in the presence of a high-affinity chelator of heavy metals, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine. The appearance of zinc occurred with or just after the rise in [Ca2+]i and was independent of Mg2+. (3) NMDA, N-methyl-DL-aspartate, or N-methyl-L-aspartate (10-200 microM) caused a slower increase in [Ca2+]i, and zinc was observed in some but not all experiments. When present, zinc appeared later than the increase in [Ca2+]i. These changes were also independent of Mg2+. (4) Decreases in both phosphocreatine and ATP were observed in all of these studies. (5) The results are discussed in terms of the proposed role of zinc as a modulator of excitotoxicity. Observations of zinc after exposure to glutamate or more slowly to NMDA, but not after depolarisation or deprivation of glucose and O2 (where increases also occur in [Ca2+]i), suggest that the cellular damage caused by the latter insults (depolarisation and fuel deprivation as in ischaemia) involves mechanisms not solely attributable to release of excitotoxins.
Badar-Goffer
R
R
Department of Physics, University of Nottingham, England.
Morris
P
P
Thatcher
N
N
Bachelard
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D016202:N-Methylaspartate / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
D005971:Glutamates; D018698:Glutamic Acid; D016202:N-Methylaspartate; D008274:Magnesium; D015032:Zinc; D002118:Calcium