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Significance Clarification of the presynaptic actions of general anesthetics is critical to understanding the molecular and cellular mechanisms of their prominent effects on synaptic transmission. We show that the ether anesthetic isoflurane inhibits synaptic vesicle exocytosis through inhibition of presynaptic Ca2+ influx in the absence of significant alteration of the Ca2+ sensitivity of exocytosis. The greater inhibition of glutamate release compared with GABA release is explained by the relative anesthetic resistance of Ca2+ influx in GABAergic boutons, consistent with overall reduction in excitatory synaptic tone.

Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca 2+ influx, not Ca 2+ -exocytosis coupling

Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca ²⁺ influx, not Ca ²⁺ -exocytosis coupling