Institute of Clinical Medicine, National Yang-Ming University school of medicine, Taiwan.
J Cardiovasc Electrophysiol. 2011 Dec;22(12):1378-86. doi: 10.1111/j.1540-8167.2011.02126.x. Epub 2011 Oct 12.
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.
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).
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.
研究心力衰竭（HF）是否通过调节钙稳态和增加晚期钠电流来增强肺静脉（PV）心律失常发生。
使用全细胞膜片钳技术研究了伴有和不伴有快速起搏诱导 HF 的兔单个 PV 心肌细胞的动作电位和离子电流。通过荧光和共聚焦显微镜评估 Ca（2+）（i）动力学。与对照 PV 心肌细胞（n=18）相比，HF PV 心肌细胞（n=13）的延迟后除极（45%对 13%，P<0.05）和自发性活动更快（3.0±0.2 对 2.1±0.2 Hz，P<0.05）。HF PV 心肌细胞的晚期 Na（+）电流、Na（+）/Ca（2+）交换电流和瞬时内向电流增加，但 Na（+）电流或 L 型钙电流减少。具有起搏活性的 HF PV 心肌细胞的 Ca（2+）（i）瞬变更大（R410/485，0.18±0.04 对 0.11±0.02，P<0.05）和肌浆网 Ca（2+）储存。此外，具有起搏活性的 HF PV 心肌细胞（n=18）的发生率更高（95%对 70%，P<0.05）、频率（7.8±3.1 对 2.3±1.2 火花/mm/s，P<0.05）、幅度（F/F（0），3.2±0.8 对 1.9±0.5，P<0.05）和更长的衰减时间（65±3 对 48±4 ms，P<0.05）。
钠和钙稳态失调以及增强的钙火花促进 HF 中 PV 心肌细胞的心律失常发生，这可能在心房颤动的发展中起重要作用。
