Effects of flecainide and quinidine on Kv4.2 currents: voltage dependence and role of S6 valines

Br J Pharmacol. 2003 Apr;138(8):1475-84. doi: 10.1038/sj.bjp.0705199.


1. The effects of flecainide and quinidine were studied on wild-type Kv4.2 channels (Kv4.2WT), channels with deletion of the N-terminal domain (N-del) and channels with mutations in the valine residues located at positions 402 and 404 in the presence (V[402,404]I) or in the absence (N-del/V[402,404]I) of the N-terminus. 2. The experiments were performed at 37 degrees C on COS7 cells using the whole-cell configuration of the patch-clamp technique. 3. Flecainide and quinidine inhibited Kv4.2WT currents in a concentration-dependent manner (IC(50)=23.6+/-1.1 and 12.0+/-1.4 microMat +50 mV, respectively), similar to their potency for the rest of the constructs at the same voltage. In Kv4.2WT channels, flecainide- and quinidine-induced block increased as channel inactivation increased. In addition, the inhibition produced by quinidine, but not by flecainide, increased significantly at positive test potentials. Similar effects were observed in N-del channels. However, in V[402,404]I and N-del/V[402,404]I channels, the voltage dependence of block by both quinidine and flecainide was lost, without significant modifications in potency at +50 mV. 4. These results point to an important role for S6 valines at positions 402 and 404 in mediating voltage-dependent block by quinidine and flecainide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Flecainide / pharmacology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mutation / physiology
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Quinidine / pharmacology*
  • Rats
  • Shal Potassium Channels
  • Valine / physiology*


  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shal Potassium Channels
  • Valine
  • Quinidine
  • Flecainide