title: Interactions of midazolam and propofol on α1β2γ2L and α1β2γ2S gamma aminobutyric acid type A receptors expressed in human embryonic kidney cells.
abstract: BACKGROUND
  The gamma aminobutyric acid type A (GABA(A)) receptor is a prime target of many anesthetics, including midazolam and propofol. Although these anesthetics have sedative and hypnotic properties by enhancing GABA(A) receptor activity, their interactions at the GABA(A) receptors have not been explored. We investigated the interaction of midazolam and propofol with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
  
  
  METHODS
  Using the whole-cell patch clamp technique, we tested the effects of midazolam and propofol on GABA-induced currents in human embryonic kidney 293 T cells transfected with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
  
  
  RESULTS
  Midazolam and propofol on their own enhanced the amplitude of GABA(A) receptor responses in a dose-dependent manner, and they had additive effects on α(1)β(2)γ(2)S GABA(A) receptors, but not on α(1)β(2)γ(2)L GABA(A) receptors. However, additive interactions of midazolam and propofol on the α(1)β(2)γ(2)L GABA(A) receptors were observed when protein kinase C was inhibited.
  
  
  CONCLUSIONS
  The interaction between midazolam and propofol is affected by receptor subtype, and protein kinase phosphorylation influences their interaction on the α(1)β(2)γ(2)L receptor.
authors.affiliation: Seoul National University Hospital, Daehakro 101, Jongno-gu, Seoul, Korea.
authors.forename: Deok Man
authors.initials: DM
authors.lastname: Hong
authors.forename: Chong Sung
authors.initials: CS
authors.lastname: Kim
authors.forename: Woosik
authors.initials: W
authors.lastname: Eom
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Oh
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Hee-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D019162:Anesthetics, Combined / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials; D008874:Midazolam / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D019162:Anesthetics, Combined; D018686:Anesthetics, Intravenous; C546279:GABRG2 protein, human; C546242:Gabra1 protein, rat; C502185:Gabrb2 protein, rat; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D011963:Receptors, GABA-A; D011493:Protein Kinase C; D008874:Midazolam; D015742:Propofol