GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital

Jahanshah Amin, David S Weiss

Research output: Contribution to journalArticle

357 Citations (Scopus)

Abstract

THE predominant inhibitory neurotrasmitter of the brain, GABA (γ-aminobutyric acid), activates chloride-selective ion pores integral to the receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel have been cloned1-4, but little information is available on the domains important for activation. Rat wild-type or mutated α1-, β2- and γ2-subiinits (designated α, β and γ) were coexpressed in Xenopus oocytes and examined electrophysiologically. We report here the identification of two separate and homologous domains of the β-subunit, each of which contributes a tyrosine and threonine essential for activation by GABA. Conservative substitution of each of these four amino acids dramatically decreased GABA channel sensitivity to activation by GABA and the GABA agonist muscimol. These substitutions, however, did not impair activation by the barbiturate pentobarbital, indicating these two different classes of agonists activate GABA channels through distinct mechanisms. We also present evidence suggesting that the two identified domains of the β-subiunit contribute a major component of the GABA receptor.

Original languageEnglish (US)
Pages (from-to)565-569
Number of pages5
JournalNature
Volume366
Issue number6455
StatePublished - Dec 9 1993
Externally publishedYes

Fingerprint

Pentobarbital
GABA-A Receptors
gamma-Aminobutyric Acid
GABA Agonists
Aminobutyrates
Muscimol
GABA Receptors
Threonine
Xenopus
Oocytes
Tyrosine
Chlorides
Ions
Amino Acids
Brain

ASJC Scopus subject areas

  • General

Cite this

GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital. / Amin, Jahanshah; Weiss, David S.

In: Nature, Vol. 366, No. 6455, 09.12.1993, p. 565-569.

Research output: Contribution to journalArticle

@article{5ec337375267409bb11397aa9f56d3fb,
title = "GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital",
abstract = "THE predominant inhibitory neurotrasmitter of the brain, GABA (γ-aminobutyric acid), activates chloride-selective ion pores integral to the receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel have been cloned1-4, but little information is available on the domains important for activation. Rat wild-type or mutated α1-, β2- and γ2-subiinits (designated α, β and γ) were coexpressed in Xenopus oocytes and examined electrophysiologically. We report here the identification of two separate and homologous domains of the β-subunit, each of which contributes a tyrosine and threonine essential for activation by GABA. Conservative substitution of each of these four amino acids dramatically decreased GABA channel sensitivity to activation by GABA and the GABA agonist muscimol. These substitutions, however, did not impair activation by the barbiturate pentobarbital, indicating these two different classes of agonists activate GABA channels through distinct mechanisms. We also present evidence suggesting that the two identified domains of the β-subiunit contribute a major component of the GABA receptor.",
author = "Jahanshah Amin and Weiss, {David S}",
year = "1993",
month = "12",
day = "9",
language = "English (US)",
volume = "366",
pages = "565--569",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6455",

}

TY - JOUR

T1 - GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital

AU - Amin, Jahanshah

AU - Weiss, David S

PY - 1993/12/9

Y1 - 1993/12/9

N2 - THE predominant inhibitory neurotrasmitter of the brain, GABA (γ-aminobutyric acid), activates chloride-selective ion pores integral to the receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel have been cloned1-4, but little information is available on the domains important for activation. Rat wild-type or mutated α1-, β2- and γ2-subiinits (designated α, β and γ) were coexpressed in Xenopus oocytes and examined electrophysiologically. We report here the identification of two separate and homologous domains of the β-subunit, each of which contributes a tyrosine and threonine essential for activation by GABA. Conservative substitution of each of these four amino acids dramatically decreased GABA channel sensitivity to activation by GABA and the GABA agonist muscimol. These substitutions, however, did not impair activation by the barbiturate pentobarbital, indicating these two different classes of agonists activate GABA channels through distinct mechanisms. We also present evidence suggesting that the two identified domains of the β-subiunit contribute a major component of the GABA receptor.

AB - THE predominant inhibitory neurotrasmitter of the brain, GABA (γ-aminobutyric acid), activates chloride-selective ion pores integral to the receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel have been cloned1-4, but little information is available on the domains important for activation. Rat wild-type or mutated α1-, β2- and γ2-subiinits (designated α, β and γ) were coexpressed in Xenopus oocytes and examined electrophysiologically. We report here the identification of two separate and homologous domains of the β-subunit, each of which contributes a tyrosine and threonine essential for activation by GABA. Conservative substitution of each of these four amino acids dramatically decreased GABA channel sensitivity to activation by GABA and the GABA agonist muscimol. These substitutions, however, did not impair activation by the barbiturate pentobarbital, indicating these two different classes of agonists activate GABA channels through distinct mechanisms. We also present evidence suggesting that the two identified domains of the β-subiunit contribute a major component of the GABA receptor.

UR - http://www.scopus.com/inward/record.url?scp=0027787023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027787023&partnerID=8YFLogxK

M3 - Article

C2 - 7504783

AN - SCOPUS:0027787023

VL - 366

SP - 565

EP - 569

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6455

ER -