Alterations of N-methyl-D-aspartate receptor properties after chemical ischemia.

Sublethal ischemic challenges can protect neurons against a second, more severe hypoxic insult. We report here that nonlethal chemical ischemia induces a transient alteration of NMDA receptors in rat cortical neurons in culture. Cells were incubated with 3 mM KCN in a glucose-free solution for 90 min.

NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurons in vitro.

The development of cortical neurons in vivo and in vitro is accompanied by alterations in NMDA receptor subunit expression and concomitant modifications in the pharmacological profile of NMDA-activated ionic currents. For example, we observed that with decreasing NR2B/NR2A subunit expression ratio, the block of NMDA receptor-mediated whole-cell responses by the NR2B-selective antagonist haloperidol was also decreased. In mature cultures (>22 d in vitro), however, NMDA responses obtained from excised nucleated macropatches, which comprised a large portion of the soma, remained strongly antagonized by haloperidol.

Subunit-specific interactions of cyanide with the N-methyl-D-aspartate receptor.

Cyanide can potentiate N-methyl-D-aspartate receptor-mediated physiological responses in neurons. Here we show that this phenomenon may be attributable to a subunit-specific chemical modification of the receptor directly by the toxin. N-Methyl-D-aspartate (30 microM)-induced whole cell responses in mature (22-29 days in vitro) rat cortical neurons were potentiated nearly 2-fold by a 3-5-min treatment with 2 mM potassium cyanide, as did a similar treatment with 4 mM dithiothreitol.

Intrinsic redox properties of N-methyl-D-aspartate receptor can determine the developmental expression of excitotoxicity in rat cortical neurons in vitro.

The sensitivity of central neurons in culture to N-methyl-D-aspartate (NMDA) receptor-mediated cell death increases with development. In this study, we show that this phenomenon in vitro may be due, at least in part, to changes in the redox properties of the NMDA receptor itself. With increasing days in culture, NMDA-induced electrical responses in rat cortical neurons are less sensitive to dithiothreitol-induced potentiation and spontaneously oxidize less readily than in younger cells.

Pharmacology of sodium-dependent high-affinity L-[3H]glutamate transport in glial cultures.

Pharmacological and molecular biological studies provide evidence for subtypes of sodium-dependent high-affinity glutamate (Glu) transport in the mammalian CNS. At least some of these transporters appear to be selectively expressed in different brain regions or by different cell types. In the present study, the properties of L-[3H]Glu transport were characterized using astrocyte-enriched cultures prepared from cerebellum and cortex.