title: [Effects of midazolam on hERG K+ channel].
abstract: OBJECTIVE
  To investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.
  
  
  METHODS
  Whole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.
  
  
  RESULTS
  Midazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.
  
  
  CONCLUSIONS
  Midazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.
authors.forename: Sheng-na
authors.initials: SN
authors.lastname: Han
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li-rong
authors.initials: LR
authors.lastname: Zhang
mesh_terms: D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D008874:Midazolam / Q000494:pharmacology*; D009154:Mutation; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D008874:Midazolam