Comparison of the effects of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K+ current of guinea-pig ventricular myocytes.
The effect of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier potassium current (IK) in guinea-pig ventricular myocytes was studied using whole cell voltage clamp techniques and under blockade of the L-type calcium current by 5 microM nitrendipine. IK consisted of two different current systems, as reported by Sanguinetti and Jurkiewicz (1990), i.e. an E4031-sensitive rapidly activating component (IKr) with a strong inward-going rectification property and an E4031-insensitive slowly activating component (IKs) with little rectification. Cibenzoline (30 microM) decreased both IKr and IKs while flecainide (10 and 30 microM) decreased the IKr exclusively. Mexiletine (30 microM), in contrast, affected neither IKr nor IKs. Since the inhibition of IK(r) and/or IKs prolongs duration of action potentials and refractory periods, class I drugs which also possess the class III effect may have additional effects in treating certain re-entrant arrhythmias.
Wang
D W
DW
Department of Physiology, Oita Medical University, Japan.
Kiyosue
T
T
Sato
T
T
Arita
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005424:Flecainide / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D008801:Mexiletine; D005424:Flecainide; D011188:Potassium; C032151:cifenline