title: Allitridin reduces I Kr current by disrupting the trafficking of human ether-à-go-go-related gene channels.
abstract: OBJECTIVE
  To investigate the effects of allitridin on human ether-à-go-go-related gene (hERG) channels.
  
  
  METHODS
  We used whole-cell patch clamping and laser confocal scanning microscopy to evaluate the effects of allitridin on hERG currents and the membrane expression of the hERG protein expressed in HEK 293 cells.
  
  
  RESULTS
  The amplitude of IKr showed a concentration-dependent decrease with increasing allitridin concentration. Additionally, alterations in the gating properties of hERG channels were also confirmed. Allitridin does not alter the voltage- and time-dependent activation of hERG channels, the gating properties of hERG channel inactivation over time or the recovery from inactivation, but allitridin does cause alterations in the steady-state inactivation and the deactivation of hERG channels. We further evaluated the influence of allitridin on membrane expression of the hERG protein. Images of allitridin-treated cells showed a reduction in hERG protein on the membrane and retention in the cytoplasm.
  
  
  CONCLUSIONS
  To the best of our knowledge this is the first study to show that allitridin reduces the IKr current by impairing the trafficking of hERG channels. The results may demonstrate that allitridin could be a promising candidate for the prevention and treatment of arrhythmia-related diseases.
authors: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Institute of Cardiovascular Channelopathy, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, and Key Laboratory of Molecular Cardiology, Xi'an, PR China.
authors: Guoliang
authors: G
authors: Li
authors: Gong
authors: G
authors: Cheng
authors: Jine
authors: J
authors: Wu
authors: Shuting
authors: S
authors: Ma
authors: Aifeng
authors: A
authors: Zhang
authors: Wenqi
authors: W
authors: Han
authors: Chaofeng
authors: C
authors: Sun
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D005737:Garlic; D057809:HEK293 Cells; D006801:Humans; D018408:Patch-Clamp Techniques; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013440:Sulfides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000498:Allyl Compounds; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013440:Sulfides; C042577:diallyl trisulfide