title: Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells.
abstract: OBJECTIVE
  Allocryptopine (ALL) is an alkaloid extracted from Corydalis decumbens (Thunb) Pers. Papaveraceae, whereas benzyltetrahydropalmatine (BTHP) is a derivative of tetrahydropalmatine extracted from Corydalis ambigua (Pall) Cham et Schlecht. The aim of this study was to investigate the effects of ALL and BTHP on the human ether-a-go-go related gene (hERG) current expressed in HEK293 cells.
  
  
  METHODS
  Cultured HEK293 cells were transiently transfected with hERG channel cDNA plasmid pcDNA3.1 using Lipofectamine. The whole-cell current IHERG was evoked and recorded using Axon MultiClamp 700B amplifier. The drugs were applied via supserfusion.
  
  
  RESULTS
  Both ALL and BTHP reversibly suppressed the amplitude and density of IHERG in concentration- and voltage-dependent manners (the respective IC50 value was 49.65 and 22.38 μmol/L). BTHP (30 μmol/L) caused a significant negative shift of the steady-state inactivation curve of IHERG, while ALL (30 μmol/L) did not affect the steady-state inactivation of IHERG. Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of IHERG. But both the drugs markedly lengthened the time constants for recovery of IHERG from inactivation. Using action potential waveform pulses, it was found that both the drugs at 30 μmol/L significantly suppressed the current densities in the late phase of action potential, but did not significantly affect the current densities in the early phase of action potential.
  
  
  CONCLUSIONS
  Both ALL and BTHP derived from Chinese herbs potently block hERG current.
authors.affiliation: Institute of Geriatric Cardiology, the General Hospital of People's Liberation Army, Beijing 100853, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lin
authors.forename: Yu-qi
authors.initials: YQ
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Jin-liao
authors.initials: JL
authors.lastname: Gao
authors.forename: Yi-cheng
authors.initials: YC
authors.lastname: Fu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xue
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D001600:Berberine Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D031311:Corydalis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D014162:Transfection
chemical_list: D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers; C060778:benzyltetrahydropalmatine; C109505:allocryptopine