GSBS Student Publications

Title

Ethanol inhibition of recombinant heteromeric NMDA channels in the presence and absence of modulators

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Pharmacology; Program in Neuroscience

Date

7-1-1995

Document Type

Article

Medical Subject Headings

Animals; Electrophysiology; Ethanol; Female; Ion Channels; Kynurenic Acid; Magnesium; N-Methylaspartate; Oxidation-Reduction; Receptors, N-Methyl-D-Aspartate; Recombinant Proteins; Xenopus laevis; Zinc

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The NMDA receptor/channel has been shown to be inhibited by ethanol in the clinically relevant range 25-100 mM. We studied heteromeric assemblies (NR1b/NR2) of the NMDA receptor, expressed in oocytes, to address three questions regarding this inhibition, and discovered the following: (1) The inhibition was nearly equivalent when ethanol was coapplied with the agonist, and when ethanol was introduced after steady-state current was established, suggesting that ethanol does not act by interfering with the activation process of the NMDA receptor. (2) The degree of inhibition was controlled by the NR2 subunit, with both NR2A and NR2B significantly more sensitive to ethanol than NR2C and NR2D. (3) Manipulation of the NMDA receptor with a number of agents that normally modulate it did not alter the degree of inhibition produced by ethanol. The presence of Mg2+ (3 and 12.5 microM), Zn2+ (1 and 10 microM), or the glycine antagonist 7-chlorokynurenic acid (1.25 or 5 microM), did not alter the ethanol sensitivity of heteromeric (NR1b/NR2A, NR1b/NR2B, NR1b/NR2C) NMDA receptors. Redox modulation of the NMDA receptor by dithiothreitol (2 mM) or 5,5'-dithiobis(2-nitrobenzoic acid) (1 mM) also did not alter the degree to which ethanol inhibits NMDA receptors. Taken together, these results indicate that the ethanol sensitivity of native NMDA receptors, which likely exist in heteromeric form, results from actions at a site different from those of known modulators of the receptor.

Rights and Permissions

Citation: J Neurochem. 1995 Jul;65(1):140-8.

Related Resources

Link to article in PubMed

Journal Title

Journal of neurochemistry

PubMed ID

7540660