title: Astragaloside IV regulates expression of ATP-sensitive potassium channel subunits after ischemia-reperfusion in rat ventricular cardiomyocytes.
abstract: OBJECTIVE
  Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the heart from myocardial ischemic injury, but the mechanisms of action are unknown. ATP-sensitive potassium (KATP) channels are activated during ischemia and exert a compensatory protective effect on cardiomyocytes. We therefore examined the effects of AsIV on KATP channel currents and channel expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion injury.
  
  
  METHODS
  Forty Wistar rats were divided into five groups: control group, ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group and IP + AsIV group. The ischemia-reperfusion injury model was established in enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The different drugs were applied for 10-15 min, and the KATP channel current (I(KATP)) was recorded with voltage-clamp mode by whole-cell patch-clamp technique. Protein and mRNA expression of the KATP channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR.
  
  
  RESULTS
  The KATP current in IP group was significantly greater than that in control group (211.45 +/- 33.67 vs 83.51 +/- 23.67 pA; P < 0.01). Glibenclamide (10 micromol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known channel opener pinacidil (50 micromol/L) significantly increased I(KATP) (P < 0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P < 0.01 vs IP group).
  
  
  CONCLUSIONS
  The protective effects of AsIV in ischemia-reperfusion injury may be related to the up-regulation of several KATP channel subunits and facilitation of KATP currents.
authors.affiliation: Scientific Research Center, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Han
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Chen
authors.forename: Jue-Feng
authors.initials: JF
authors.lastname: Cai
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D054086:KATP Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000008:administration & dosage*; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D004365:Drugs, Chinese Herbal; D054086:KATP Channels; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A