Structural and functional basis for GABAA receptor heterogeneity.
When gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in vertebrate brain, binds to its receptor it activates a chloride channel. Neurotransmitter action at the GABAA receptor is potentiated by both benzodiazepines and barbiturates which are therapeutically useful drugs (reviewed in ref. 1). There is strong evidence that this receptor is heterogeneous. We have previously isolated complementary DNAs encoding an alpha- and a beta-subunit and shown that both are needed for expression of a functional GABAA receptor. We have now isolated cDNAs encoding two additional GABAA receptor alpha-subunits, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating a molecular basis for it. These alpha-subunits are differentially expressed within the CNS and produce, when expressed with the beta-subunit in Xenopus oocytes, receptor subtypes which can be distinguished by their apparent sensitivity to GABA. Highly homologous receptor subtypes which differ functionally seem to be a common feature of brain receptors.
Levitan
E S
ES
MRC Molecular Neurobiology Unit, MRC Centre, Cambridge, UK.
Schofield
P R
PR
Burt
D R
DR
Rhee
L M
LM
Wisden
W
W
Köhler
M
M
Fujita
N
N
Rodriguez
H F
HF
Stephenson
A
A
Darlison
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D011963:Receptors, GABA-A / Q000235:genetics; D014981:Xenopus
D011963:Receptors, GABA-A; D004247:DNA