Am J Psychiatry 1991; 148:162-173
Copyright © 1991 by American Psychiatric Association
Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry
CF Zorumski and KE Isenberg
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
OBJECTIVE: As a result of combined biophysical and molecular biological
studies, important insights into the structure and function of gamma-
aminobutyric acid (GABA) receptors have been achieved. These insights have
helped to define the role of GABA receptors in synaptic inhibition and the
ion channel mechanisms by which different neuropsychiatric drugs work. The
authors' goal is to describe the actions of GABA as a neurotransmitter and
discuss the modulation of receptor function by different drugs. DATA
COLLECTION: The authors focus on more recent studies of the structure and
physiology of the receptor-ion channel complex and the relevance of these
studies to psychiatry. FINDINGS: The CNS effects of benzodiazepines,
barbiturates, and alcohol have been linked to the GABA-chloride channel
receptor complex. Multiple subunits of this complex have been cloned,
sequenced, and expressed in heterologous systems. The results of cloning
studies, coupled with membrane biophysics, have provided important insights
into the structure and function of GABA receptors and their modulation by
psychopharmacological agents. CONCLUSIONS: Future understanding of disease
states, drug effects, and therapeutic successes and failures may be
expressed in terms of differences in the structure and function of specific
receptors and their associated ion channels. Furthermore, the ability to
describe the molecular function of receptor subtypes offers the ability to
tailor drug specificity by developing agents directed against a given
receptor subtype. The current GABA studies also have important implications
for the understanding of how neurotransmitter systems may be involved in
illness.
