18/8/2017 Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions.

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Enflurane decreases glutamate neurotransmission to spinal cord

motor neurons by both pre- and postsynaptic actions.
Anesthesia and Analgesia. 96(5):1354-9, Table of Contents, MAY 2003

Gong Cheng; Joan J Kendig

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Abstract
UNLABELLED
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 alpha-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 alpha-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

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18/8/2017 Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions.

uniformly depressed by multiple mechanisms, whereas some anesthetic actions tend to enhance
inhibition.

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