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

研究成果: 雜誌貢獻文章

64 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)915-925
頁數11
期刊British Journal of Pharmacology
153
發行號5
DOIs
出版狀態已發佈 - 三月 2008

    指紋

ASJC Scopus subject areas

  • Pharmacology

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