The GABAA receptor: An important target for the general anaesthetic etomidate

J. J. Lambert; A. R. Haythornthwaite; D. R. Peden; M. B. Herd; K. A. Wafford; T. W. Rosahl; D. Belelli

doi:10.1016/j.ics.2005.07.071

The GABAA receptor: An important target for the general anaesthetic etomidate

J. J. Lambert (Lead / Corresponding author), A. R. Haythornthwaite, D. R. Peden, M. B. Herd, K. A. Wafford, T. W. Rosahl, D. Belelli

Systems Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

The general anaesthetic etomidate potently and selectively enhances the function of the GABA_A receptor. Furthermore, etomidate is selective for GABA_A receptors that incorporate a β₂ or a β₃ subunit, but is relatively ineffective at equivalent receptors containing the β₁ subunit. This selectivity is governed by the nature of a single amino acid residue (asparagine, N for β₂ and β₃; serine, S for β₁). Utilising this knowledge gene targeting was used to create a mouse in which the β₂ subunit was engineered to be relatively insensitive to etomidate (β_2N265S). In Purkinje neurones derived from such mice, the effects of etomidate on inhibitory synaptic transmission are greatly reduced. In complementary behavioural experiments, the mutation influences both the sedative and hypnotic actions of etomidate.

Original language	English
Pages (from-to)	67-72
Number of pages	6
Journal	International Congress Series
Volume	1283
DOIs	https://doi.org/10.1016/j.ics.2005.07.071
Publication status	Published - Nov 2005

Keywords

Etomidate
GABA
GABA receptor
General anaesthetic
Sedation

ASJC Scopus subject areas

Medicine(all)

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10.1016/j.ics.2005.07.071

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title = "The GABAA receptor: An important target for the general anaesthetic etomidate",

abstract = "The general anaesthetic etomidate potently and selectively enhances the function of the GABAA receptor. Furthermore, etomidate is selective for GABAA receptors that incorporate a β2 or a β3 subunit, but is relatively ineffective at equivalent receptors containing the β1 subunit. This selectivity is governed by the nature of a single amino acid residue (asparagine, N for β2 and β3; serine, S for β1). Utilising this knowledge gene targeting was used to create a mouse in which the β2 subunit was engineered to be relatively insensitive to etomidate (β2N265S). In Purkinje neurones derived from such mice, the effects of etomidate on inhibitory synaptic transmission are greatly reduced. In complementary behavioural experiments, the mutation influences both the sedative and hypnotic actions of etomidate.",

keywords = "Etomidate, GABA, GABA receptor, General anaesthetic, Sedation",

author = "Lambert, {J. J.} and Haythornthwaite, {A. R.} and Peden, {D. R.} and Herd, {M. B.} and Wafford, {K. A.} and Rosahl, {T. W.} and D. Belelli",

year = "2005",

month = nov,

doi = "10.1016/j.ics.2005.07.071",

language = "English",

volume = "1283",

pages = "67--72",

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TY - JOUR

T1 - The GABAA receptor

T2 - An important target for the general anaesthetic etomidate

AU - Lambert, J. J.

AU - Haythornthwaite, A. R.

AU - Peden, D. R.

AU - Herd, M. B.

AU - Wafford, K. A.

AU - Rosahl, T. W.

AU - Belelli, D.

PY - 2005/11

Y1 - 2005/11

N2 - The general anaesthetic etomidate potently and selectively enhances the function of the GABAA receptor. Furthermore, etomidate is selective for GABAA receptors that incorporate a β2 or a β3 subunit, but is relatively ineffective at equivalent receptors containing the β1 subunit. This selectivity is governed by the nature of a single amino acid residue (asparagine, N for β2 and β3; serine, S for β1). Utilising this knowledge gene targeting was used to create a mouse in which the β2 subunit was engineered to be relatively insensitive to etomidate (β2N265S). In Purkinje neurones derived from such mice, the effects of etomidate on inhibitory synaptic transmission are greatly reduced. In complementary behavioural experiments, the mutation influences both the sedative and hypnotic actions of etomidate.

AB - The general anaesthetic etomidate potently and selectively enhances the function of the GABAA receptor. Furthermore, etomidate is selective for GABAA receptors that incorporate a β2 or a β3 subunit, but is relatively ineffective at equivalent receptors containing the β1 subunit. This selectivity is governed by the nature of a single amino acid residue (asparagine, N for β2 and β3; serine, S for β1). Utilising this knowledge gene targeting was used to create a mouse in which the β2 subunit was engineered to be relatively insensitive to etomidate (β2N265S). In Purkinje neurones derived from such mice, the effects of etomidate on inhibitory synaptic transmission are greatly reduced. In complementary behavioural experiments, the mutation influences both the sedative and hypnotic actions of etomidate.

KW - Etomidate

KW - GABA

KW - GABA receptor

KW - General anaesthetic

KW - Sedation

U2 - 10.1016/j.ics.2005.07.071

DO - 10.1016/j.ics.2005.07.071

M3 - Article

AN - SCOPUS:33646543364

SN - 0531-5131

VL - 1283

SP - 67

EP - 72

JO - International Congress Series

JF - International Congress Series

ER -

The GABAA receptor: An important target for the general anaesthetic etomidate

Abstract

Keywords

ASJC Scopus subject areas

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