Macrokinetic analysis of blockade of NMDA-gated currents by substituted alcohols, alkanes and ethers.

Volatile hydrocarbon based CNS depressants including short chain alcohols and anesthetics act, in part, by inhibition of the excitatory effect of glutamate at the NMDA receptor. While effects of several of these volatile agents on NMDA-gated currents have been demonstrated, there has been no direct comparison of different chemical classes of CNS depressant drugs on NMDA-gated currents. Here, whole-cell voltage clamp measurements of currents gated by 100 microM NMDA from cultured cerebrocortical neurons were examined in the presence of varying concentrations of the alcohols ethanol and hexanol, the halogenated alcohol trichloroethanol, the halogenated alkane halothane and the halogenated ethers isoflurane and sevoflurane.

Comparison of effect of ethanol on N-methyl-D-aspartate- and GABA-gated currents from acutely dissociated neurons: absence of regional differences in sensitivity to ethanol.

In vivo, ethanol alters the effect of N-methyl-D-aspartate (NMDA) and GABA in some brain regions but is without effect in others. To determine whether these regional differences were due to differences in the effect of ethanol on postsynaptic NMDA or GABAA receptors, we examined the effect of ethanol on NMDA- and GABA-gated currents from neurons acutely dissociated from the lateral septal nucleus, substantia nigra, thalamus, hippocampus, and cerebellum. Ethanol decreased the effect of NMDA similarly in all brain areas tested and had similar effects on Chinese hamster ovary cells expressing NR2A or NR2B subunits with an NR1-1a subunit.

Changes in the effect of isoflurane on N-methyl-D-aspartic acid-gated currents in cultured cerebral cortical neurons with time in culture: evidence for subunit specificity.

Background: Developmental changes in NR1 splice variants and NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor have been associated with changes in the sensitivity of NMDA receptors to agonists, antagonists, and pharmacologic modulators. The authors have investigated changes in the effect of isoflurane on NMDA-gated currents from cultured cortical neurons with time in culture and related these changes to the subunit composition of the NMDA receptors.

Methods: N-methyl-D-aspartate-gated currents were measured using whole-cell voltage clamp recording in cortical neurons cultured for 1-4 weeks and HEK 293 cells transiently expressing NR1-1a + NR2A or NR1-1a + NR2B subunit-containing receptors.