A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors

J E Dalziel; Bryndis Birnir; A B Everitt; M L Tierney; G B Cox; P W Gage

doi:10.1016/S0014-2999(99)00138-7

A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors

J E Dalziel, Bryndis Birnir, A B Everitt, M L Tierney, G B Cox, P W Gage

External Organization - Unknown

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.

Originalspråk	engelska
Sidor (från-till)	345-348
Tidskrift	European Journal of Pharmacology
Volym	370
Nummer	3
DOI	https://doi.org/10.1016/S0014-2999(99)00138-7
Status	Published - 1999
Externt publicerad	Ja

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)

Ämnesklassifikation (UKÄ)

Farmakologi och toxikologi

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10.1016/S0014-2999(99)00138-7

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@article{5cb75855182a45d09804793540861a07,

title = "A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors",

abstract = "Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.",

keywords = "M2 transmembrane segment, Ligand-gated, GABAA receptor, human, Sf9 cell, Desensitization, Receptor assembly",

author = "Dalziel, {J E} and Bryndis Birnir and Everitt, {A B} and Tierney, {M L} and Cox, {G B} and Gage, {P W}",

note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)",

year = "1999",

doi = "10.1016/S0014-2999(99)00138-7",

language = "English",

volume = "370",

pages = "345--348",

journal = "European Journal of Pharmacology",

issn = "1879-0712",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors

AU - Dalziel, J E

AU - Birnir, Bryndis

AU - Everitt, A B

AU - Tierney, M L

AU - Cox, G B

AU - Gage, P W

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)

PY - 1999

Y1 - 1999

N2 - Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.

AB - Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.

KW - M2 transmembrane segment

KW - Ligand-gated

KW - GABAA receptor

KW - human

KW - Sf9 cell

KW - Desensitization

KW - Receptor assembly

U2 - 10.1016/S0014-2999(99)00138-7

DO - 10.1016/S0014-2999(99)00138-7

M3 - Article

SN - 1879-0712

VL - 370

SP - 345

EP - 348

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 3

ER -

A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors

Sammanfattning

Bibliografisk information

Ämnesklassifikation (UKÄ)

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