General Anesthesia Based on Recent Mechanism Hypothesis

Abstract

  GABA is the principal inhibitory neurotransmitter in the central nerve system. It mediates fast synaptic inhibition by interaction with the GABA_A receptor. GABA_A receptors are ligand-gated ion channels that are modulated by a large number of anesthetics. Over the past decade, in addition to conventional forms of transient synaptic responses that underlie phasic conductances, a tonic conductance has been identified in several brain regions. Tonic inhibition of this type refers to the continuous activation of high affinity, slowly desensitizing GABA_A receptors by low concentrations of ambient GABA. For many years, enhancement of fast synaptic inhibition was widely thought to be the primary mechanism underlying the actions of many anesthetics. Recently, attention has turned to tonic inhibition, as this conductance has more sensitivity to anesthetic actions than phasic inhibition. Here we summarize several recent discoveries related to the effects of anesthetics on GABA_A receptors.