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Halothane acts as a partial agonist of the α6β2γ2S GABAA receptor
Author(s) -
Sincoff Robert,
Tanguy Joëlle,
Hamilton Beverly,
Carter Don,
Brunner Edward A.,
Yeh Jay Z.
Publication year - 1996
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.10.13.8940300
Subject(s) - bicuculline , picrotoxin , gabaa receptor , halothane , chemistry , agonist , muscimol , biophysics , receptor , antagonist , gamma aminobutyric acid , pharmacology , biochemistry , biology , organic chemistry
Whole‐cell patch clamp recording was performed on human embryonic kidney 293 cells stably transfected with rat cDNAs for the α6, β2, and γ2S subunits of the GABAA receptor. The volatile anesthetic halothane directly activated a current in the absence of the ligand γ‐aminobutyric acid (GABA). Both the current amplitude and the rate of desensitization increased in a dose‐dependent manner with an EC 50 of 1.0±0.2 mM and a Hill coefficient (nh) of 1.5±0.1. The EC 50 and nh for GABA to activate the receptor were 1.0±0.3 μM and 1.4±0.2, respectively. The peak amplitude of the halothane‐activated current was about 4% of the maximal GABA response, which was not changed when the concentration of Ca 2+ in the external solution was decreased from 2 mM to 0.2 mM. The reversal potential of both halothane‐ and GABA‐activated currents changed with the external Cl. concentration as predicted by the Nernst equation for chloride ions. The halothane‐ and GABA‐activated currents were blocked by both the noncompetitive GABAA receptor antagonist pi‐ crotoxin and the competitive GABAA receptor an‐tagonist bicuculline. Schild plots revealed that the K is for bicuculline to competitively antagonize the currents activated by halothane and GABA are similar (0.69 and 0.72 μM, respectively). These results indicate that halothane activates the α6β2γ2S GABAA receptor to induce a current similar to the GABA‐induced current.—Sincoff, R., Tanguy, J., Hamilton, B., Carter, D., Brunner, E. A., Yeh, J. Z. Halothane acts as a partial agonist of the α6β2γ2S GABAA receptor. FASEB J. 10,1539‐1545 (1996)