Effect of amiodarone on Kv1.4 channel C-type inactivation: comparison of its effects with those induced by propafenone and verapamil.
As the major component of I(to) (slow), Kv1.4 channel plays an important role in repolarization of cardiac myocytes. C-type inactivation is one of Kv1.4 inactivation and can be affected by open channel blockers. We used the two-electrode voltage clamp technique to observe the effect of amiodarone on Kv1.4 C-type inactivation and compare amiodarone's effects on Kv1.4 with propafenone and verapamil. Our data show that those three antiarrhythmic drugs blocked fKv1.4 delta N (N-terminal deleted Kv1.4 channel from ferret heart) in voltage- and frequent-dependent manners. The amiodarone's IC50 was 489.23 +/- 4.72 microM, higher than that of propafenone (98.97 +/- 1.13 microM) and verapamil (263.26 +/- 6.89 microM) for fKv1.4 delta N channel (+50 mV). After application of amiodarone, propafenone and verapamil, fKv1.4 delta N inactivation becomes bi-exponential: the faster portion of inactivation (drug-induced inactivation) and the slower portion of inactivation (C-type inactivation). Amiodarone and verapamil fastened C-type inactivation in fKv1.4 delta N, but propafenone did not. Unlike propafenone that had no effect on fKv1.4 delta N recovery, amiodarone and verapamil slowed recovery in fKv1.4 delta N.
Xu
L
L
Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.
Huang
C
C
Chen
J
J
Jiang
X
X
Li
X
X
Bett
G C L
GC
Rasmusson
R L
RL
Wang
S
S
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D051665:Kv1.4 Potassium Channel / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011405:Propafenone / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*; D029867:Xenopus Proteins / Q000187:drug effects*; D014982:Xenopus laevis
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D018076:DNA, Complementary; D051665:Kv1.4 Potassium Channel; C496980:Kv1.4 potassium channel, Xenopus; D029867:Xenopus Proteins; D011405:Propafenone; D014700:Verapamil; D000638:Amiodarone