title: Effect of K201, a novel antiarrhythmic drug on calcium handling and arrhythmogenic activity of pulmonary vein cardiomyocytes.
abstract: OBJECTIVE
  Pulmonary veins are the most important focus for the generation of atrial fibrillation. Abnormal calcium homeostasis with ryanodine receptor dysfunction may underlie the arrhythmogenic activity in pulmonary veins. The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. The purpose of this study was to investigate the effects of K201 on the arrhythmogenic activity and calcium regulation of pulmonary vein cardiomyocytes.
  
  
  METHODS
  The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes from rabbit pulmonary vein before and after the administration of K201, by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques.
  
  
  RESULTS
  K201 (0.1, 0.3, 1 microM) reduced the firing rates in pulmonary vein cardiomyocytes, decreased the amplitudes of the delayed afterdepolarizations and prolonged the action potential duration. K201 decreased the L-type calcium currents, Na(+)/Ca(2+) exchanger currents, transient inward currents and calcium transients. K201 (1 microM, but not 0.1 microM or 0.3 microM) also reduced the sarcoplasmic reticulum calcium content. Moreover, both the pretreatment and administration of K201 (0.3 microM) decreased the isoprenaline (10 nM)-induced arrhythmogenesis in pulmonary veins.
  
  
  CONCLUSIONS
  K201 reduced the arrhythmogenic activity of pulmonary vein cardiomyocytes and attenuated the arrhythmogenicity induced by isoprenaline. These findings may reveal the anti-arrhythmic potential of K201.
authors.affiliation: Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan. a9900112@,s15.hinet.net
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Chen
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Wongcharoen
authors.forename: C-I
authors.initials: CI
authors.lastname: Lin
authors.forename: S-A
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; C109183:K201 compound; D007545:Isoproterenol; D002118:Calcium