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ANESTHETIC PHARMACOLOGY

Enflurane Decreases Glutamate Neurotransmission to Spinal Cord Motor Neurons by Both Pre- and Postsynaptic Actions

Department of Anesthesia, Stanford University School of Medicine, Stanford, California

Address correspondence to Joan J. Kendig, MD, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305. Address e-mail to kendig{at}stanford.edu

We have previously reported volatile anesthetic actions on glycinergic inhibitory transmission to spinal motor neurons. The present study is a comparable set of experiments on glutamatergic excitatory transmission. We tested the hypothesis that the balance between excitation and inhibition is shifted toward inhibition by larger depressant actions on excitation. Patch-clamp techniques were used to study spontaneous and evoked glutamate -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid currents in rat spinal cord slices. Enflurane (0.6 mM, 1 minimum alveolar anesthetic concentration) significantly decreased spontaneous miniature current frequencies either when sodium channels were blocked (miniature excitatory postsynaptic currents, mEPSCs), or when sodium channels were not blocked (spontaneous excitatory postsynaptic currents, sEPSCs). Enflurane did not affect mEPSC or sEPSC amplitude or kinetics. The effects on mEPSCs and sEPSCs did not differ. Enflurane significantly decreased both amplitude and area of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-evoked currents with no change in kinetics (P < 0.05 and 0.01, respectively). In contrast, enflurane increased miniature glycinergic current frequency when sodium channels were blocked, and prolonged glycinergic current duration. Enflurane actions on glutamatergic excitatory transmission are purely depressant both pre- and postsynaptically, whereas glycinergic inhibition is enhanced presynaptically under some conditions, and always prolonged postsynaptically. Thus, enflurane shifts the balance between synaptic excitation and inhibition in the direction of inhibition.

IMPLICATIONS: Explanations proposed for anesthetic-induced central nervous system depression include enhancement of synaptic inhibition and depression of excitation. The results reported herein suggest that, in the case of enflurane, the mechanism is a shift in the balance toward inhibition. Excitation is uniformly depressed by multiple mechanisms, whereas some anesthetic actions tend to enhance inhibition.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999