title: Heart failure enhanced pulmonary vein arrhythmogenesis and dysregulated sodium and calcium homeostasis with increased calcium sparks.
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.
  
  
  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.
authors: Institute of Clinical Medicine, National Yang-Ming University school of medicine, Taiwan.
authors: Shih-Lin
authors: SL
authors: Chang
authors: Yao-Chang
authors: YC
authors: Chen
authors: Yung-Hsin
authors: YH
authors: Yeh
authors: Yung-Kuo
authors: YK
authors: Lin
authors: Tsu-Juey
authors: TJ
authors: Wu
authors: Cheng-I
authors: CI
authors: Lin
authors: Shih-Ann
authors: SA
authors: Chen
authors: Yi-Jen
authors: YJ
authors: Chen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002118:Calcium / Q000378:metabolism*; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D006706:Homeostasis; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology; D011667:Pulmonary Veins / Q000503:physiopathology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium; D002118:Calcium