Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes

Shih Huang Lee, Yao Chang Chen, Yi J. Chen, Shih L. Chang, Ching T. Tai, Wanwarang Wongcharoen, Hung I. Yeh, Cheng I. Lin, Shih A. Chen

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1806-1815
Number of pages10
JournalLife Sciences
Volume80
Issue number19
DOIs
Publication statusPublished - Apr 17 2007

Fingerprint

Pulmonary Veins
Cardiac Myocytes
Tumor Necrosis Factor-alpha
Calcium
Sarcoplasmic Reticulum
Atrial Fibrillation
Adenosine Triphosphatases
Homeostasis
Inflammation
Clamping devices
Action Potentials
Cardiac Arrhythmias
Western Blotting
Cytokines
Rabbits

Keywords

  • Atrial fibrillation
  • Calcium transient
  • Pulmonary vein
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes. / Lee, Shih Huang; Chen, Yao Chang; Chen, Yi J.; Chang, Shih L.; Tai, Ching T.; Wongcharoen, Wanwarang; Yeh, Hung I.; Lin, Cheng I.; Chen, Shih A.

In: Life Sciences, Vol. 80, No. 19, 17.04.2007, p. 1806-1815.

Research output: Contribution to journalArticle

Lee, SH, Chen, YC, Chen, YJ, Chang, SL, Tai, CT, Wongcharoen, W, Yeh, HI, Lin, CI & Chen, SA 2007, 'Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes', Life Sciences, vol. 80, no. 19, pp. 1806-1815. https://doi.org/10.1016/j.lfs.2007.02.029
Lee, Shih Huang ; Chen, Yao Chang ; Chen, Yi J. ; Chang, Shih L. ; Tai, Ching T. ; Wongcharoen, Wanwarang ; Yeh, Hung I. ; Lin, Cheng I. ; Chen, Shih A. / Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes. In: Life Sciences. 2007 ; Vol. 80, No. 19. pp. 1806-1815.
@article{36dbe5f709f0421ea50c9e170b029280,
title = "Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes",
abstract = "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.",
keywords = "Atrial fibrillation, Calcium transient, Pulmonary vein, Tumor necrosis factor-α",
author = "Lee, {Shih Huang} and Chen, {Yao Chang} and Chen, {Yi J.} and Chang, {Shih L.} and Tai, {Ching T.} and Wanwarang Wongcharoen and Yeh, {Hung I.} and Lin, {Cheng I.} and Chen, {Shih A.}",
year = "2007",
month = "4",
day = "17",
doi = "10.1016/j.lfs.2007.02.029",
language = "English",
volume = "80",
pages = "1806--1815",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "19",

}

TY - JOUR

T1 - Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes

AU - Lee, Shih Huang

AU - Chen, Yao Chang

AU - Chen, Yi J.

AU - Chang, Shih L.

AU - Tai, Ching T.

AU - Wongcharoen, Wanwarang

AU - Yeh, Hung I.

AU - Lin, Cheng I.

AU - Chen, Shih A.

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

UR - http://www.scopus.com/inward/record.url?scp=34047270092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047270092&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2007.02.029

DO - 10.1016/j.lfs.2007.02.029

M3 - Article

C2 - 17383682

AN - SCOPUS:34047270092

VL - 80

SP - 1806

EP - 1815

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 19

ER -