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 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 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.