Effects of Intravenous and Volatile anesthetics on synaptic potentials in hippocampal slices of the rat

In order to assess the mechanism (s) of general anesthetics in the central nervous system, we studied the effects of intravenous (thiopental, pentobarbital, propofol) and volatile (isoflurane, sevoflurane, enflurane) anesthetics on synaptic potentials of Schaffer collateral fibers input to CA1 pyramidal neurons in rat hippocampal slices. Transverse hippocampal slices (400 μm) were obtained from male Wister rats (100-200 g) by standard methods. Field excitatory postsynaptic potetials (EPSPs and popultation spikes (PSs) were elicited with a bipolar nichrome electrode placed on Schaffer collateral fibers and were recorded at area CA1 with a 3-5 MΩ glass-microelectrode. Intravenous anesthetics were directly dissolved into ACSF. Volatile anesthetics were vaporized with a specific vaporizer and then bubbled into ACSF. Intravenous and Volatile anesthetics decreased the PS amplitudes in a concentration-dependent manner without a change in EPSP slopes. Paired-pulse experiments revealed that volatile anesthetics significantly enhanced the paired-pulse faclitation (PPF) and that intravenous anesthetics reduced the PPF. Intravenous anesthetics (not volatile anesthetics) induced use-dependent changes of PS amplitudes but volatile anesthetics did not. The effects of intravenous anesthetics were blocked by bicuculline methiodide (50 μM, GABA(A) antagonist). However bicuculline faded to completely blocked the actions of volatile anesthetics. The effects of muscimol (20μM, GABA(A) agonist) on PS amplitudes were similar to those of volatile anesthetics. We suspected that intravenus anesthetics may inhibit the GABA uptake process or increase the GABA release process in inhibitory interneurons terminals, and that the depletion of GABA in terminals resulted in use-dependent changes of PS amplitude. Volatile anesthetics may directly affect on GABA(A) receptor, but additional factors may be involved in their actons.