Tags

Type your tag names separated by a space and hit enter

Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors.
J Pharmacol Exp Ther. 1999 Jul; 290(1):362-7.JP

Abstract

Ethanol is a general anesthetic agent as defined by abolition of movement in response to noxious stimulation. This anesthetic endpoint is due to spinal anesthetic actions. This study was designed to test the hypothesis that ethanol acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Whole cell recordings were made in visually identified motor neurons in spinal cord slices from 14- to 23-day-old rats. Currents were evoked by stimulating a dorsal root fragment or by brief pulses of glutamate. Ethanol at general anesthetic concentrations (50-200 mM) depressed both responses. Ethanol also depressed glutamate-evoked responses in the presence of tetrodotoxin (300 nM), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acidA and glycine receptors by bicuculline (50 microM) and strychnine (5 microM), respectively, did not significantly reduce the effects of ethanol on glutamate currents. Ethanol also depressed glutamate-evoked currents when the inhibitory receptors were blocked and either D, L-2-amino-5-phosphonopentanoic acid (40 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 microM) were applied to block N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, respectively. The results show that ethanol exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acidA and glycine inhibition is not required for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.

Links

Publisher Full Text

Authors+Show Affiliations

Wang MY
Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA.
Rampil IJ
No affiliation info available
Kendig JJ
No affiliation info available

MeSH

AnestheticsAnimalsChloride ChannelsDepression, ChemicalElectric StimulationEthanolExcitatory Postsynaptic PotentialsIn Vitro TechniquesMotor NeuronsPatch-Clamp TechniquesRatsRats, Sprague-DawleyReceptors, AMPAReceptors, GABA-AReceptors, GlycineReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10381800

Citation

Wang, M Y., et al. "Ethanol Directly Depresses AMPA and NMDA Glutamate Currents in Spinal Cord Motor Neurons Independent of Actions On GABAA or Glycine Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 1, 1999, pp. 362-7.
Wang MY, Rampil IJ, Kendig JJ. Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors. J Pharmacol Exp Ther. 1999;290(1):362-7.
Wang, M. Y., Rampil, I. J., & Kendig, J. J. (1999). Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors. The Journal of Pharmacology and Experimental Therapeutics, 290(1), 362-7.
Wang MY, Rampil IJ, Kendig JJ. Ethanol Directly Depresses AMPA and NMDA Glutamate Currents in Spinal Cord Motor Neurons Independent of Actions On GABAA or Glycine Receptors. J Pharmacol Exp Ther. 1999;290(1):362-7. PubMed PMID: 10381800.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors. AU - Wang,M Y, AU - Rampil,I J, AU - Kendig,J J, PY - 1999/6/25/pubmed PY - 1999/6/25/medline PY - 1999/6/25/entrez SP - 362 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 290 IS - 1 N2 - Ethanol is a general anesthetic agent as defined by abolition of movement in response to noxious stimulation. This anesthetic endpoint is due to spinal anesthetic actions. This study was designed to test the hypothesis that ethanol acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Whole cell recordings were made in visually identified motor neurons in spinal cord slices from 14- to 23-day-old rats. Currents were evoked by stimulating a dorsal root fragment or by brief pulses of glutamate. Ethanol at general anesthetic concentrations (50-200 mM) depressed both responses. Ethanol also depressed glutamate-evoked responses in the presence of tetrodotoxin (300 nM), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acidA and glycine receptors by bicuculline (50 microM) and strychnine (5 microM), respectively, did not significantly reduce the effects of ethanol on glutamate currents. Ethanol also depressed glutamate-evoked currents when the inhibitory receptors were blocked and either D, L-2-amino-5-phosphonopentanoic acid (40 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 microM) were applied to block N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, respectively. The results show that ethanol exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acidA and glycine inhibition is not required for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10381800/Ethanol_directly_depresses_AMPA_and_NMDA_glutamate_currents_in_spinal_cord_motor_neurons_independent_of_actions_on_GABAA_or_glycine_receptors_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10381800 DB - PRIME DP - Unbound Medicine ER -