TY - JOUR
T1 - Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes
AU - Lee, Szu-Chih
AU - Chen, Yao Chang
AU - Chen, Yi Jen
AU - Chang, Shih Lin
AU - Tai, Ching Tai
AU - Wongcharoen, Wanwarang
AU - Yeh, Hung I.
AU - Lin, Cheng I.
AU - Chen, Shih Ann
N1 - Funding Information:
The present work was supported by grants NSC 94–2314-B-010–053, NSC 94–2314-B-010–056, NSC 94–2314-B-075–093, VGH92–238, VGH92–243, VGH 94–005, VGH 94–009, VGH 94–204, VGH 94–206, VTY 92-P5–34, VTY92-P5–29, SKH-TMU-92–12 from Shin Kong Wu Ho-Su Memorial Hospital, and MMH E-94003 from Mackay Memorial Hospital. Professor Winstone W. Shen gave editing comments on a previous version of this manuscript.
PY - 2007/4/17
Y1 - 2007/4/17
N2 - Inflammation and abnormal calcium homeostasis play important roles in atrial fibrillation. Tumor necrosis factor-α (TNFα), a proinflammatory cytokine, can induce cardiac arrhythmias. Pulmonary veins (PVs) are critical in initiating paroxysmal atrial fibrillation. This study was designed to investigate whether TNFα may change the calcium handling and arrhythmogenic activity of PV cardiomyocytes. We used whole-cell patch clamp and indo-1 fluorimetric ratio technique to investigate the action potentials, ionic currents and intracellular calcium in isolated rabbit single PV cardiomyocytes with and without (control) incubation with TNFα (25 ng/ml) for 7-10 h. The expression of sarcoplasmic reticulum ATPase in the control and TNFα-treated PV cardiomyocytes was evaluated by confocal micrographs and Western blot. We found that the spontaneous beating rates were similar between the control (n = 45) and TNFα-treated (n = 28) PV cardiomyocytes. Compared with the control PV cardiomyocytes, the TNFα-treated PV cardiomyocytes had significantly a larger amplitude of the delayed afterdepolarizations (6.0 ± 1.7 vs. 2.6 ± 0.8 mV, P < 0.05), smaller L-type calcium currents, larger transient inward currents, larger Na+-Ca2+ exchanger currents, a smaller intracellular calcium transient, smaller sarcoplasmic reticulum calcium content, larger diastolic intracellular calcium, a longer decay portion of the calcium transient (Tau), and a decreased sarcoplasmic reticulum ATPase expression. In conclusion, TNFα can increase the PV arrhythmogenicity and induce an abnormal calcium homeostasis, thereby causing inflammation-related atrial fibrillation.
AB - Inflammation and abnormal calcium homeostasis play important roles in atrial fibrillation. Tumor necrosis factor-α (TNFα), a proinflammatory cytokine, can induce cardiac arrhythmias. Pulmonary veins (PVs) are critical in initiating paroxysmal atrial fibrillation. This study was designed to investigate whether TNFα may change the calcium handling and arrhythmogenic activity of PV cardiomyocytes. We used whole-cell patch clamp and indo-1 fluorimetric ratio technique to investigate the action potentials, ionic currents and intracellular calcium in isolated rabbit single PV cardiomyocytes with and without (control) incubation with TNFα (25 ng/ml) for 7-10 h. The expression of sarcoplasmic reticulum ATPase in the control and TNFα-treated PV cardiomyocytes was evaluated by confocal micrographs and Western blot. We found that the spontaneous beating rates were similar between the control (n = 45) and TNFα-treated (n = 28) PV cardiomyocytes. Compared with the control PV cardiomyocytes, the TNFα-treated PV cardiomyocytes had significantly a larger amplitude of the delayed afterdepolarizations (6.0 ± 1.7 vs. 2.6 ± 0.8 mV, P < 0.05), smaller L-type calcium currents, larger transient inward currents, larger Na+-Ca2+ exchanger currents, a smaller intracellular calcium transient, smaller sarcoplasmic reticulum calcium content, larger diastolic intracellular calcium, a longer decay portion of the calcium transient (Tau), and a decreased sarcoplasmic reticulum ATPase expression. In conclusion, TNFα can increase the PV arrhythmogenicity and induce an abnormal calcium homeostasis, thereby causing inflammation-related atrial fibrillation.
KW - Atrial fibrillation
KW - Calcium transient
KW - Pulmonary vein
KW - Tumor necrosis factor-α
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U2 - 10.1016/j.lfs.2007.02.029
DO - 10.1016/j.lfs.2007.02.029
M3 - Article
C2 - 17383682
AN - SCOPUS:34047270092
SN - 0024-3205
VL - 80
SP - 1806
EP - 1815
JO - Life Sciences
JF - Life Sciences
IS - 19
ER -