title: Intravenous anesthetic propofol inhibits multiple human cardiac potassium channels.
abstract: BACKGROUND
  Propofol is widely used clinically for the induction and maintenance of anesthesia. Clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. The current study investigates the effects of propofol on human cardiac potassium channels.
  
  
  METHODS
  The whole cell patch voltage clamp technique was used to record transient outward potassium current (Ito) and ultrarapidly activating delayed rectifier potassium current (IKur) in human atrial myocytes and hKv1.5, human ether-à-go-go-related gene (hERG), and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells. Current clamp mode was used to record action potentials in human atrial myocytes.
  
  
  RESULTS
  In human atrial myocytes, propofol inhibited Ito in a concentration-dependent manner (IC50 = 33.5 ± 2.0 μM for peak current, n = 6) by blocking open channels without affecting the voltage-dependent kinetics or the recovery time constant; propofol decreased IKur (IC50 = 35.3 ± 1.9 μM, n = 6) in human atrial myocytes and inhibited hKv1.5 current expressed in HEK 293 cells by preferentially binding to the open channels. Action potential duration at 90% repolarization was slightly prolonged by 30 μM propofol in human atrial myocytes. In addition, propofol also suppressed hERG and hKCNQ1/hKCNE1 channels expressed in HEK 293 cells.
  
  
  CONCLUSIONS
  Propofol inhibits multiple human cardiac potassium channels, including human atrial Ito and IKur, as well as hKv1.5, hERG, and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, and slightly prolongs human atrial action potential duration, which may contribute to the antiatrial tachycardia/fibrillation effects observed in patients who receive propofol.
authors.affiliation: From the Department of Anesthesiology, Union Hospital (L.Y.), Department of Pharmacology (H.L.), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; and Department of Physiology (L.Y., H.L., G.-R.L.) and Department of Medicine (H.-Y.S., G.-R.L.), Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: D000368:Aged; D018686:Anesthetics, Intravenous; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000008:administration & dosage*; D015221:Potassium Channels / Q000502:physiology*; D015742:Propofol / Q000008:administration & dosage*
chemical_list: D018686:Anesthetics, Intravenous; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015742:Propofol