title: Effects of diltiazem and propafenone on the inactivation and recovery kinetics of fKv1.4 channel currents expressed in Xenopus oocytes.
abstract: OBJECTIVE
  To investigate the effects of diltiazem, an L-type calcium channel blocker, and propafenone, a sodium channel blocker, on the inactivation and recovery kinetics of fKv1.4, a potassium channel that generates the cardiac transient outward potassium current.
  
  
  METHODS
  The cRNA for fKv1.4ΔN, an N-terminal deleted mutant of the ferret Kv1.4 potassium channel, was injected into Xenopus oocytes to express the fKv1.4ΔN channel in these cells. Currents were recorded using a two electrode voltage clamp technique.
  
  
  RESULTS
  Diltiazem (10 to 1000 μmol/L) inhibited the fKv1.4ΔN channel in a frequency-dependent, voltage-dependent, and concentration-dependent manner, suggesting an open channel block. The IC(50) was 241.04±23.06 μmol/L for the fKv1.4ΔN channel (at +50 mV), and propafenone (10 to 500 μmol/L) showed a similar effect (IC(50)=103.68±10.13 μmol/L). After application of diltiazem and propafenone, fKv1.4ΔN inactivation was bi-exponential, with a faster drug-induced inactivation and a slower C-type inactivation. Diltiazem increased the C-type inactivation rate and slowed recovery in fKv1.4ΔN channels. However, propafenone had no effect on either the slow inactivation time constant or the recovery.
  
  
  CONCLUSIONS
  Diltiazem and propafenone accelerate the inactivation of the Kv1.4ΔN channel by binding to the open state of the channel. Unlike propafenone, diltiazem slows the recovery of the Kv1.4ΔN channel.
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China. vividcurio@yahoo.com.cn
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Shi-min
authors.initials: SM
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Jiang
authors.forename: Sheng-ping
authors.initials: SP
authors.lastname: Chao
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051665:Kv1.4 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011405:Propafenone / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D002317:Cardiovascular Agents; D051665:Kv1.4 Potassium Channel; D011994:Recombinant Proteins; D011405:Propafenone; D004110:Diltiazem