ZINC-DEFICIENCY DECREASES THE CONCENTRATION OF N-METHYL-D-ASPARTATE RECEPTORS IN GUINEA-PIG CORTICAL SYNAPTIC-MEMBRANES

Zinc deficiency in guinea pigs decreases glutamate-stimulated calcium uptake in cortical synap tosomes. Glutamate not only stimulates calciu m uptake but also potentiates the binding of the drug dizocilpine (MK- 801) to an internal site of the N-methyl-D-aspartate receptor/calcium channel, a subtype of the glutamate receptor. The purpose of this stud y was to determine whether the effect of zinc deficiency on calcium up take by glutamate-stimulated synaptosomes is related to N-methyl-D-asp artate receptor number or function, as measured by MK-801 binding. Imm ature guinea pigs consumed a low zinc (<1 mg/kg) diet ad libitum or an adequate zinc (100 mg/kg) diet, either ad libitum or restricted to ma intain weight similar to that of the low zinc animals. Binding of MK-8 01 to cortical membranes was measured first in the presence of saturat ing concentrations of glutamate or N-methyl-D-aspartate in combination with glycine. Zinc deficiency significantly reduced the concentration of MK-801 binding sites (20%) regardless of the potentiating agonist used, but had no effect on binding affinity. The binding of MK-801 in response to 1, 10 and 100 mu mol/L glycine, in the presence of 100 nmo l/L glutamate, was then measured and found to be significantly reduced (12%). The results suggest that zinc deficiency decreases the number of functional N-methyl-D-aspartate receptor/channels in cortical membr anes, probably because of impaired channel opening.