The effect of sevoflurane on glutamate release and uptake in rat cerebrocortical presynaptic terminals.
BACKGROUND
Volatile anaesthetics exert their effect in the brain mainly by reducing synaptic excitability. Isoflurane abates excitation by reducing the release and increasing the uptake of transmitter glutamate into the presynaptic terminal. The exact molecular mechanisms exerting these effects, however, are not clear. Voltage-gated calcium channels have been proposed as the pharmacological target. The present study examines the effect of sevoflurane on synaptic glutamate release and free cytosolic calcium and the effect on high- and low-affinity uptake of L-glutamate using isolated presynaptic terminals prepared from rat cerebral cortex.


METHODS
Released glutamate was measured fluorometrically in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. 4-aminopyridine was used to induce membrane depolarization. Glutamate uptake was measured in a series of different concentrations of L-glutamate corresponding to the high- and the low- affinity uptake systems adding a fixed concentration og radiolabelled glutamate. The labelling was measured by counting disintegrations per min in a beta-scintillation counter.


RESULTS
Sevoflurane reduced the calcium-dependent glutamate release in a dose-dependent manner as sevoflurane 1.5, 2.5 and 4.0% reduced the release by 58, 69 and 94%, respectively (P<0.05). Membrane depolarization induced an increase in free cytosolic calcium by 25%. Sevoflurane did not affect this increase. Neither the high- nor the low-affinity uptake transporter systems are affected by the anaesthetic.


CONCLUSIONS
These results indicate that different volatile anaesthetics may act differently on the presynaptic terminal. The exact modes of action have to be further investigated.
Vinje
M L
ML
Institute for Surgical Research and Department of Neurosurgery, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. mortenla@klinmed.uio.no
Moe
M C
MC
Valø
E T
ET
Berg-Johnsen
J
J
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008738:Methyl Ethers / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013574:Synaptosomes / Q000378:metabolism
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D018698:Glutamic Acid; D002118:Calcium