Heart Failure Enhanced Pulmonary Vein Arrhythmogenesis and Dysregulated Sodium and Calcium Homeostasis with Increased Calcium Sparks

Institute of Clinical Medicine, National Yang-Ming University school of medicine, Taiwan.
Journal of Cardiovascular Electrophysiology (Impact Factor: 3.48). 12/2011; 22(12):1378-86. DOI: 10.1111/j.1540-8167.2011.02126.x
Source: PubMed

ABSTRACT Late sodium currents and intracellular Ca(2+) (Ca(2+) (i)) dynamics play an important role in arrhythmogenesis of pulmonary vein (PV) and heart failure (HF). It is not clear whether HF enhances PV arrhythmogenesis through modulation of Ca(2+) homeostasis and increased late sodium currents. The aim of this study was to investigate the sodium and calcium homeostasis in PV cardiomyocytes with HF. METHODS AND RESULTS: Whole-cell patch clamp was used to investigate the action potentials and ionic currents in isolated rabbit single PV cardiomyocytes with and without rapid pacing induced HF. The Ca(2+) (i) dynamics were evaluated through fluorescence and confocal microscopy. As compared to control PV cardiomyocytes (n = 18), HF PV cardiomyocytes (n = 13) had a higher incidence of delayed afterdepolarization (45% vs 13%, P < 0.05) and faster spontaneous activity (3.0 ± 0.2 vs 2.1 ± 0.2 Hz, P < 0.05). HF PV cardiomyocytes had increased late Na(+) currents, Na(+) /Ca(2+) exchanger currents, and transient inward currents, but had decreased Na(+) currents or L-type calcium currents. HF PV cardiomyocytes with pacemaker activity had larger Ca(2+) (i) transients (R410/485, 0.18 ± 0.04 vs 0.11 ± 0.02, P < 0.05), and sarcoplasmic reticulum Ca(2+) stores. Moreover, HF PV cardiomyocytes with pacemaker activity (n = 18) had higher incidence (95% vs 70%, P < 0.05), frequency (7.8 ± 3.1 vs 2.3 ± 1.2 spark/mm/s, P < 0.05), amplitude (F/F(0) , 3.2 ± 0.8 vs 1.9 ± 0.5, P < 0.05), and longer decay time (65 ± 3 vs 48 ± 4 ms, P < 0.05) of Ca(2+) sparks than control PV cardiomyocytes with pacemaker activity (n = 18). CONCLUSIONS: Dysregulated sodium and calcium homeostasis, and enhanced calcium sparks promote arrhythmogenesis of PV cardiomyocytes in HF, which may play an important role in the development of atrial fibrillation.

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