Agent-selective effects of volatile anesthetics on GABA(A) receptor-mediated synaptic inhibition in hippocampal interneurons

Background: A relatively small number of inhibitory interneurons can contro l the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of i nterneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthet ics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneu rons. Methods: Pharmacologically Isolated gamma -aminobutyric acid type A (GABA(A )) receptor-mediated IPSCs were recorded with whole cell, patch-damp techni ques In visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region wer e studied, The effects of clinically relevant concentrations (1.0 rat minim um alveolar concentration) of halothane, enflurane, isoflurane, and sevoflu rane were compared on kinetics of both stimulus-evoked and spontaneous GABA (A) receptor-mediated IPSCs in interneurons. Results: Halothane (1.2 vol% approximate to 0.35 mM), enflurane (2.2 vol% a pproximate to 0.60 mM), isoflurane (1.4 vol% approximate to 0.50 mM), and s evoflurane (2.7 vol% approximate to 0.40 mM) preferentially depressed evoke d IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6 ), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addi tion, all anesthetics differentially prolonged the decay time constant of e voked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negati ve charge transfer mediated by GABA(A) receptors between synaptically conne cted interneurons was enhanced by all anesthetics. Conclusions: Volatile anesthetics differentially enhanced GABA(A) receptor- mediated synaptic inhibition in rat hippocampal interneurons, suggesting th at hippocampal interneuron circuits are depressed by these anesthetics in a n agent-specific manner.