Mechanisms of GABA-A and GABA-B receptor gene expression

DAVID FARB,; JANINE STEIGER,; MARIA CLARA GRAVIELLE; STELLA MARTIN,; TERRELL GIBBS,; SHELLEY RUSSEK,

The GABA receptor

The Humana Press

Lugar: New York; Año: 2007; p. 169 - 235

The γ-aminobutyric acid (GABA) neurotransmitter acting through ionotropic and metabotropic receptor classes exerts the major inhibitory control in the central nervous system. Therapeutic agents targeting GABA receptors (GABA-R), such as benzodiazepines and baclofen, are used to treat many nervous system conditions, including anxiety and spasticity. The subunit composition of GABA-Rs at the cell surface plays a critical role in determining their physiological and pharmacological properties, and alteration of GABA-R subunit expression has been associated with a number of diseases including schizophrenia, temporal lobe epilepsy, and alcoholism. The ionotropic type A GABA receptor (GABAAR) and type C GABA receptor (GABACR) are pentameric complexes that comprise a ligand gated chloride channel. The metabotropic type B GABA receptor (GABABR) is a heterodimer that couples G protein-signaling to GABA binding. There are eight classes of ionotropic receptor subunits and only two metabotropic receptor subunit classes. Most of the GABAAR subunit genes are localized in syntenic β-α-γ gene clusters on four chromosomes but the two GABABR genes are localized on distinct chromosomes. Control over subunit expression in different brain regions and during development is orchestrated at the genomic level by the use of multiple promoter regions and through the alternative splicing of GABA-R subunit RNAs. This chapter examines current GABA-R research relevant to the many levels of control over receptor gene regulation and cell surface receptor expression that may be relevant to both health and disease.