Halothane-induced desensitization of α1β2γ2S and α6β2γ2S GABAA receptors expressed in HEK293 cells

K. Nishikawa*, T. Mori, J. Z. Yeh, T. Narahashi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Inahalational general anesthetics are known to exert a dual action on the GABAA receptor, potentiation and suppression. Whereas potentiation is regarded as one of the most important mechanisms of anesthesia, the role of GABAA receptor suppression remains to be seen. Methods: GABA-induced currents were recorded by the whole-cell patch clamp technique from HEK cells expressing the α1β2γ2S and α6β2γ2S subunits, and the effects of halothane were examined. Results: The EC50 and the Hill coefficient (nH) were estimated to be 10.5 μM and 1.40, respectively, for the α1β2γ2S subunits, and 1.07 μM and 1.63, respectively, for the α6β2γ2S subunits. Preperfusion of halothane for 3 min suppressed or desensitized currents induced by a high concentration of GABA (3 × EC50) with the IC50s and nHs of 0.84 mM and 1.61, respectively, for the α1β2γ2S, and 0.93 mM and 2.57, respectively, for the α6β2γ2S. Halothane 0.9 mM genarated a small current in the α6β2γ2S subunit. The time courses of halothane inhibition and recovery after washout resemble the time course of GABA-induced desensitization, GABA-induced receptor desensitization was further enhanced by halothane due to a shift of GABA desensitization curve in the direction of low concentrations of GABA, and the shift was more pronounced in α1β2γ2S than α6β2γ2S. Conclusions: Halothane-induced desensitization was observed when it was preperfused and tested by high concentrations of GABA, conditions that colosely resemble those in vivo since halothane is continuously administered to the patient and the concentration of GABA released from nerve terminals is very high (≥ 500 μM) at the synaptic cleft. Since high concentrations of halothane is used during induction and also since desensitization of GABAA receptors could lead to disinhibition, halothane desensitization may play an important role in excitement of the patient observed before surgical anesthesia sets in.

Original languageEnglish (US)
Pages (from-to)159-160
Number of pages2
JournalAnesthesia and Resuscitation
Issue number4
StatePublished - 2000


  • Desensitization
  • GABA receptor
  • Halothane

ASJC Scopus subject areas

  • Emergency Medicine
  • Anesthesiology and Pain Medicine


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