Introduction

Most seizures are relatively brief and self-terminating. During some seizures, however, early termination fails and status epilepticus (SE) ensues. One hypothesis for the development of SE is that activation of γ-aminobutyric acid (GABA) receptor-mediated inhibition is responsible for normal termination of a seizure. If the GABAergic inhibition fails to terminate the seizure, a progressive reduction of GABA_A receptor-mediated inhibition develops that, when severe enough, results in a prolonged self-sustained seizure (24). There is experimental support for this hypothesis. Prolonged hippocampal seizures reduce GABA receptor-mediated inhibition (20), and this reduction of inhibition can reliably predict the occurrence of SE (20). The treatment of SE in humans also suggests a role for GABA receptors, since SE is treated with the benzodiazepines diazepam, lorazepam, and midazolam and the barbiturates phenobarbital and pentobarbital, all of which exert their anticonvulsant effect by enhancing GABA-mediated inhibition (65). The GABA receptor is the site of action of many of the antiepileptic drugs used to treat SE in humans, and there is direct evidence of altered properties of hippocampal GABA receptors during SE. Thus, it is important to characterize the functional properties of GABA receptors and the effect of SE on these properties in order to understand the pathogenesis and treatment of SE.