Effect of K201, a novel antiarrhythmic drug on calcium handling and arrhythmogenic activity of pulmonary vein cardiomyocytes

Y. J. Chen, Y. C. Chen, W. Wongcharoen, C. I. Lin, S. A. Chen

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background and purpose: 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. Experimental approach: 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. Key results: K201 (0.1, 0.3, 1 μM) 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 μM, but not 0.1 μM or 0.3 μM) also reduced the sarcoplasmic reticulum calcium content. Moreover, both the pretreatment and administration of K201 (0.3 μM) decreased the isoprenaline (10 nM)-induced arrhythmogenesis in pulmonary veins. Conclusions and implications: 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.

Original languageEnglish
Pages (from-to)915-925
Number of pages11
JournalBritish Journal of Pharmacology
Volume153
Issue number5
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Atrial fibrillation
  • Calcium handling
  • Pulmonary vein
  • Ryanodine receptor
  • Triggered activity

ASJC Scopus subject areas

  • Pharmacology

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