title: Comparison of the effects of antiarrhythmic drugs flecainide and verapamil on fKv1.4ΔN channel currents in Xenopus oocytes.
abstract: OBJECTIVE
  To study the effects of Na(+) channel blocker flecainide and L-type Ca(2+) channel antagonist verapamil on the voltage-gated fKv1.4ΔN channel, an N-terminal-deleted mutant of the ferret Kv1.4 K(+) channel.
  
  
  METHODS
  fKv1.4ΔN channels were stably expressed in Xenopus oocytes. The K(+) currents were recorded using a two-electrode voltage-clamp technique. The drugs were administered through superfusion.
  
  
  RESULTS
  fKv1.4ΔN currents displayed slow inactivation, with a half-inactivation potential of -41.74 mV and a slow recovery from inactivation (τ=1.90 s at -90 mV). Flecainide and verapamil blocked the currents with IC(50) values of 512.29 ± 56.92 and 260.71 ± 18.50 μmol/L, respectively. The blocking action of the drugs showed opposite voltage-dependence: it was enhanced with depolarization for flecainide, and was attenuated with depolarization for verapamil. Both the drugs exerted state-dependent blockade on fKv1.4ΔN currents, but verapamil showed a stronger use-dependent blockage compared with flecainide. Flecainide accelerated the C-type inactivation rate without affecting the recovery kinetics and the steady-state activation. Verapamil also accelerated the inactivation kinetics of the currents, but unlike flecainide, it affected both the recovery and the steady-state activation, causing slower recovery of fKv1.4ΔN channel and a depolarizing shift of the steady-state activation curve.
  
  
  CONCLUSIONS
  The results demonstrate that widely used antiarrhythmic drugs flecainide and verapamil substantially inhibit fKv1.4ΔN channels expressed in Xenopus oocytes by binding to the open state of the channels. Therefore, caution should be taken when these drugs are administered in combination with K(+) channel blockers to treat arrhythmia.
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Sheng-ping
authors.initials: SP
authors.lastname: Chao
authors.forename: Jiang-hua
authors.initials: JH
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Jiang
authors.forename: Shi-min
authors.initials: SM
authors.lastname: Wang
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D015870:Gene Expression; D051665:Kv1.4 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D000889:Anti-Arrhythmia Agents; D051665:Kv1.4 Potassium Channel; D014700:Verapamil; D005424:Flecainide