title: Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes.
abstract: BACKGROUND
  The blockade of cardiac transmembrane potassium channels, which is commonly seen with various antiarrhythmic drugs, plays an important role in their mechanism of action. We studied and compared the less-explored effects of three Class IA antiarrhythmics on the transient outward current (I(to)) and on the inward rectifier (I(kl)), ATP sensitive (I(KATP)), and delayed rectifier (I(K)) potassium currents in rabbit ventricular myocytes.
  
  
  RESULTS
  Transmembrane currents were measured by applying the whole-cell configuration of the patch-clamp technique at 37 degrees C in myocytes enzymatically isolated from rabbit ventricular preparations. Quinidine (10 microM), disopyramide (10 microM), and procainamide (50 microM) were studied at concentrations close to or exceeding the therapeutic plasma level. All studied drugs significantly decreased the amplitude of I(KATP) (activated by 50 microM pinacidil) and I(K) currents. None of them influenced significantly I(kl). The amplitude of I(to) was decreased by quinidine and disopyramide but was not considerably altered by procainamide. The fast inactivation of I(to) was not changed by procainamide and was significantly accelerated by quinidine and disopyramide.
  
  
  CONCLUSIONS
  Although quinidine, disopyramide, and procainamide are all classified as Class IA antiarrhythmics, these drugs had different effects on various potassium currents, which may partially explain their distinct effect on repolarization in various cardiac tissues and on cardiac arrhythmias in clinical settings.
authors.affiliation: Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, Albert Szent-Györgyi Medical Center, University of Szeged, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Iost
authors.forename: László
authors.initials: L
authors.lastname: Virág
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D004206:Disopyramide / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011342:Procainamide / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D000255:Adenosine Triphosphate; D004206:Disopyramide; D011802:Quinidine; D011342:Procainamide