Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions

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 mini-mum 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 a-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 4s enhanced presynaptically under some conditions, and always prolonged postsynaptically. Thus, enflurane shifts the balance between synaptic excitation and inhibition in the direction of inhibition.