title: [Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits].
abstract: OBJECTIVE
  To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits.
  
  
  METHODS
  Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv).
  
  
  RESULTS
  (1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P < 0.05). BmKIM prolonged the recovery of inactivation of I(Na). In the presence of BmKIM, the time constants of recovery (both tau(f) and tau(s)) of I(Na) were significantly prolonged from (28.9 +/- 6.1) ms and (107 +/- 21.6) ms in control group to (54.2 +/- 7.9) ms (P < 0.05) and (211.1 +/- 34.6) ms (P < 0.01), respectively. (2) BmKIM significantly shortened 50% and 90% of action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01).
  
  
  CONCLUSIONS
  BmKIM significantly blocked I(Na) through affecting the inactivated state of I(Na) in rabbit ventricular myocytes. BmKIM could attenuate the influx of I(Na), therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Geng-Shan
authors.initials: GS
authors.lastname: Li
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; C467987:BmKIM peptide; D010455:Peptides; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D015222:Sodium Channels