EFFECTS OF SMALL CONCENTRATIONS OF VOLATILE ANESTHETICS ON ACTION-POTENTIAL FIRING OF NEOCORTICAL NEURONS IN-VITRO

Background: Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- curren ts flowing across the gamma-aminobutyric acid(A) (GABA(A)) receptor-io n channel complex. The extent to which an increase hi GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing mu st be determined, because many further effects of these agents have be en reported on the molecular level. Methods: The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons we re investigated by extracellular recordings in organotypic slice cultu res derived from the rat neocortex. Results: Volatile anesthetics depr essed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concent ration (EC50) values were about one half the EC50 values for general a nesthesia. In the presence of the GABA(A) antagonist bicuculline (20 m u M), the effectiveness of halothane, isoflurane, and enflurane In red ucing the discharge rates were diminished by 48-65%, indicating that t hese drugs act via the GABA(A) receptor. Conclusions: Together with re cent investigations, our results provide evidence that halothane, isof lurane, and enflurane reduced spontaneous action potential firing of n eocortical neurons in cultured brain slices mainly by increasing GABA( A)-mediated synaptic inhibition, At concentrations, approximately one half the EC (50) for general anesthesia, volatile anesthetics increase d overall GABA(A)-mediated synaptic inhibition about twofold, thus dec reasing spontaneous action potential firing by half.