title: Blocking effect of methylflavonolamine on human Na(V)1.5 channels expressed in Xenopus laevis oocytes and on sodium currents in rabbit ventricular myocytes.
abstract: OBJECTIVE
  To investigate the blocking effects of methylflavonolamine (MFA) on human Na(V)1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (I(Na)) in rabbit ventricular myocytes.
  
  
  METHODS
  Human Na(V)1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. I(Na) and action potentials in rabbit ventricular myocytes were studied using the whole-cell recording.
  
  
  RESULTS
  MFA and lidocaine inhibited human Na(V)1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with IC(50) values of 72.61 micromol/L and 145.62 micromol/L, respectively. Both of them markedly shifted the steady-state activation curve of I(Na) toward more positive potentials, shifted the steady-state inactivation curve of I(Na) toward more negative potentials and postponed the recovery of the I(Na) inactivation state. In rabbit ventricular myocytes, MFA inhibited I(Na) with a shift in the steady-state inactivation curve toward more negative potentials, thereby postponing the recovery of the I(Na) inactivation state. This shift was in a positive rate-dependent manner. Under current-clamp mode, MAF significantly decreased action potential amplitude (APA) and maximal depolarization velocity (V(max)) and shortened action potential duration (APD), but did not alter the resting membrane potential (RMP). The demonstrated that the kinetics of sodium channel blockage by MFA resemble those of class I antiarrhythmic agents such as lidocaine.
  
  
  CONCLUSIONS
  MFA protects the heart against arrhythmias by its blocking effect on sodium channels.
authors.affiliation: Medical College of Wuhan University of Science and Technology, China.
authors.forename: Xin-rong
authors.initials: XR
authors.lastname: Fan
authors.forename: Ji-hua
authors.initials: JH
authors.lastname: Ma
authors.forename: Pei-hua
authors.initials: PH
authors.lastname: Zhang
authors.forename: Jun-lian
authors.initials: JL
authors.lastname: Xing
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D044948:Flavonols / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009865:Oocytes / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D044948:Flavonols; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; C052073:SIPI 549; D008012:Lidocaine; D012964:Sodium