Neuropharmacology
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The volatile anesthetics enhance GABAergic inhibitory transmission at synaptic and extrasynaptic sites at central neurons. In the present study, we investigated the effects of three volatile anesthetics (isoflurane, enflurane and sevoflurane) on synaptic and extrasynaptic GABA(A) receptor responses using mechanically dissociated rat hippocampal CA1 neurons in which functional native nerve endings (boutons) were retained. The extrasynaptic GABA(A) receptors were activated by exogenous GABA application while synaptic ones were assessed by miniature and evoked inhibitory postsynaptic currents (mIPSCs and eIPSCs, respectively). ⋯ For GABAergic eIPSCs, both isoflurane and enflurane decreased the evoked response amplitude and increased the failure rate (Rf), while sevoflurane decreased the amplitude without affecting Rf. These results suggest that isoflurane and enflurane at the clinically relevant concentrations predominantly act on GABAergic presynaptic nerve endings to decrease action potential dependent GABA release. It was concluded that these anesthetics have heterogeneous effects on mIPSCs and eIPSCs with different modulation of synaptic and extrasynaptic GABA(A) receptors.