title: Effect of mexiletine on long QT syndrome model.
abstract: OBJECTIVE
  To make a LQT3 model (one form of the long QT syndromes) and to investigate the effect of mexiletine on LQT3.
  
  
  METHODS
  Sea anemone toxin (ATX II) was used to produce the LQT3 model. The Effect of mexiletine on LQT3 was performed on single Na channel, action potential, and electrocardiography in guinea pigs.
  
  
  RESULTS
  With the binding of ATX II to the Na+ channels, the probability of being in the open state and the open time constant of single Na+ channel with long opening mode increased significantly. Action potential duration APD50, APD90, and the maximal upstroke velocity of phase 0 were increased by 25.8 %, 26.1 %, and 12 %, respectively. The QT interval and QTc, a rectified QT interval, increased by 12.8 % and 16.9 %. On the contrary, after application of mexiletine, the open probability of single Na+ channel was reduced greatly. In the presence of ATX II (40 nmol/L), mexiletine (1, 5, 15, 45, 70 micromol/L) shortened the APD50 by 0.5 %, 6.7 %, 14.4 %, 19.4 %, and 18.8 %, respectively, and decreased the APD90 and Vmax accordingly. In the experiments with ECG, mexiletine reversed the ATX II-produced prolongation effects on QTc in a dose-dependent manner.
  
  
  CONCLUSIONS
  Mexiletine may be an effective drug in the treatment of LQT3.
authors.affiliation: Department of Physiology, Shanghai Second Medical University, Shanghai 200025, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Yan-Qian
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Yang
authors.forename: Ci-Zhen
authors.initials: CZ
authors.lastname: Li
authors.forename: Yuan-Mou
authors.initials: YM
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002469:Cell Separation; D003064:Cnidarian Venoms / Q000302:isolation & purification; D004562:Electrocardiography / Q000187:drug effects; D006168:Guinea Pigs; D008133:Long QT Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008801:Mexiletine / Q000627:therapeutic use*; D009206:Myocardium / Q000166:cytology; D012615:Sea Anemones / Q000737:chemistry; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D003064:Cnidarian Venoms; D015222:Sodium Channels; D008801:Mexiletine