Journal article
The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations
British journal of pharmacology, Vol.129(4), pp.731-743
02/2000
DOI: 10.1038/sj.bjp.0703087
PMCID: PMC1571881
PMID: 10683198
Abstract
The actions of 13 general anaesthetics (diethyl ether, enflurane, isoflurane, methoxyflurane, sevoflurane, chloral hydrate, trifluoroethanol, tribromoethanol,
tert
-butanol, chloretone, brometone, trichloroethylene, and α-chloralose) were studied on agonist-activated Cl
−
currents at human GABA
A
α
2
β
1
, glycine α
1
, and GABA
C
ρ
1
receptors expressed in human embryonic kidney 293 cells.
All 13 anaesthetics enhanced responses to submaximal (EC
20
) concentrations of agonist at GABA
A
and glycine receptors, except α-chloralose, which did not enhance responses at the glycine α
1
receptor. None of the anaesthetics studied potentiated GABA responses at the GABA
C
ρ
1
receptor.
Potentiation of submaximal agonist currents by the anaesthetics was studied at GABA
A
and glycine receptors harbouring mutations in putative transmembrane domains 2 and 3 within GABA
A
α
2
, β
1
, or glycine α
1
receptor subunits: GABA
A
α
2
(S270I)β
1
, α
2
(A291W)β
1
, α
2
β
1
(S265I), and α
2
β
1
(M286W); glycine α
1
(S267I) and α
1
(A288W). For all anaesthetics studied except α-chloralose, at least one of the mutations above abolished drug potentiation of agonist responses at GABA
A
and glycine receptors.
α-Chloralose produced efficacious direct activation of the GABA
A
α
2
β
1
receptor (a ‘GABA-mimetic' effect). The other 12 anaesthetics produced minimal or no direct activation of GABA
A
and glycine receptors. A non-anaesthetic isomer of α-chloralose, β-chloralose, was inactive at GABA
A
and glycine receptors and did not antagonize the actions of α-chloralose at GABA
A
receptors.
The implications of these findings for the molecular mechanisms of action of general anaesthetics at GABA
A
and glycine receptors are discussed.
Details
- Title: Subtitle
- The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations
- Creators
- Matthew D Krasowski - Committee on Neurobiology, University of Chicago, Whitman Laboratory, 915 East 57th Street, Chicago, Illinois, IL 60637, U.S.ANeil L Harrison - Department of Anesthesia and Critical Care, Whitman Laboratory, 915 East 57th Street, Chicago, Illinois, IL 60637, U.S.A
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.129(4), pp.731-743
- DOI
- 10.1038/sj.bjp.0703087
- PMID
- 10683198
- PMCID
- PMC1571881
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 02/2000
- Academic Unit
- Pathology
- Record Identifier
- 9984047627502771
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