Journal article
Trichloroethanol modulation of recombinant GABAA, glycine and GABA rho 1 receptors
The Journal of pharmacology and experimental therapeutics, Vol.284(3), pp.934-942
03/1998
DOI: 10.1016/S0022-3565(24)37323-9
PMID: 9495852
Abstract
The actions of 2,2,2,-trichloroethanol were studied on agonist-activated Cl- currents in gamma-aminobutyric acid type A (GABAA), glycine and GABA rho 1 receptors by use of the whole-cell patch-clamp technique. Recombinant wild-type and mutant receptor subunits were transiently expressed in human embryonic kidney (HEK) 293 cells. Trichloroethanol enhanced currents elicited by submaximal (EC20) agonist concentrations at GABAA alpha 2 beta 1 receptors and glycine alpha 1 homomeric receptors in a reversible, concentration-dependent manner. Trichloroethanol, at concentrations of < or = 2 mM, did not significantly alter the magnitude of submaximal GABA currents at GABA rho 1 receptors, whereas higher concentrations inhibited submaximal GABA currents. Recent work has identified residues within putative transmembrane domains 2 and 3 as critical for positive modulation of GABAA and glycine receptors by n-alkanols and volatile ether anesthetics. Submaximal glycine currents at receptors containing either of two specific mutations within the glycine receptor alpha 1 subunit (S267I and A288W) were not enhanced by low concentrations of trichloroethanol and were inhibited by higher concentrations of trichloroethanol. In the GABAA alpha 2 beta 1 receptor, a specific mutation within transmembrane domain 3 of the beta 1 subunit (M286W) also abolished positive modulation by trichloroethanol. Mutations within the GABAA alpha 2 receptor subunit did not alter positive modulation by TCEt, whereas such mutations ablate positive modulation by n-alkanols and volatile anesthetics. In summary, trichloroethanol modulation of GABAA, glycine and GABA rho 1 receptors shares some, but not all, features in common with the requirements for modulation by n-alkanols and volatile anesthetics.
Details
- Title: Subtitle
- Trichloroethanol modulation of recombinant GABAA, glycine and GABA rho 1 receptors
- Creators
- Matthew D Krasowski - Department of Anesthesia and Critical Care, University of Chicago, Illinois, USA. kra3@harper.uchicago.eduSuzanne E FinnQing YeNeil L Harrison
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.284(3), pp.934-942
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(24)37323-9
- PMID
- 9495852
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Grant note
- GM56850 / NIGMS NIH HHS GM00623 / NIGMS NIH HHS GM45129 / NIGMS NIH HHS
- Language
- English
- Date published
- 03/1998
- Academic Unit
- Pathology
- Record Identifier
- 9984047855302771
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