ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes

Yu Hsun Kao, Jung Chieh Hsu, Yao Chang Chen, Yung Kuo Lin, Baigalmaa Lkhagva, Shih Ann Chen, Yi Jen Chen

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

Background ZFHX3 plays an important role in the genesis of atrial fibrillation. However, the atrial electrophysiological effects of ZFHX3 are not clear. This study sought to investigate roles of ZFHX3 in atrial electrophysiology and calcium homeostasis by using HL-1 atrial myocytes knocked-down with ZFHX3. Methods Patch clamp, confocal fluorescence microscopy and Western blot were used to study electrical activity, ionic currents, calcium homeostasis and protein expressions in stable ZFHX3 shRNA cells. Results As compared to control, ZFHX3 shRNA cells with 28% decline of ZFHX3 protein had a larger sarcoplasmic reticulum Ca2+ content by 62%, Ca2+ transient by 20%, and calcium leak by 75%. ZFHX3 shRNA cells (n = 35) had shorter action potential duration (APD) at 50% (14.7 ± 0.9 versus 20.3 ± 1.4 ms, P <0.005), and 20% (6.1 ± 0.3 versus 8.3 ± 0.8 ms, P <0.005) repolarization than control cells (n = 30). ZFHX3 shRNA cells (n = 10) had larger amplitudes of isoproterenol (1 μM)-induced delayed afterdepolarization (14.1 ± 0.9 versus 7.2 ± 0.2 mV, P <0.05) than control cells (n = 10). Besides, acetylcholine (3 μM) shortened APD at 90% repolarization to a greater extent (19 ± 4% versus 7 ± 2%, P <0.01) in ZFHX3 shRNA cells (n = 11) than in control cells (n = 12). In addition, ZFHX3 shRNA cells had increased expressions of SERCA2a, ryanodine receptor, Kv1.4, Kv1.5 and Kir3.4. Moreover, ZFHX3 shRNA cells had a larger SERCA2a activity, ultra-rapid delayed rectifier potassium currents, transient outward currents and acetylcholine-sensitive potassium currents. Conclusions ZFHX3 knock-down in atrial myocytes dysregulated calcium homeostasis and increased atrial arrhythmogenesis, which may contribute to the occurrence of AF.
原文英語
頁(從 - 到)85-92
頁數8
期刊International Journal of Cardiology
210
DOIs
出版狀態已發佈 - 五月 1 2016

指紋

Muscle Cells
Homeostasis
Calcium
Small Interfering RNA
Action Potentials
Acetylcholine
Potassium
Ryanodine Receptor Calcium Release Channel
Electrophysiology
Sarcoplasmic Reticulum
Isoproterenol
Fluorescence Microscopy
Confocal Microscopy
Atrial Fibrillation
Proteins
Western Blotting

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此文

ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes. / Kao, Yu Hsun; Hsu, Jung Chieh; Chen, Yao Chang; Lin, Yung Kuo; Lkhagva, Baigalmaa; Chen, Shih Ann; Chen, Yi Jen.

於: International Journal of Cardiology, 卷 210, 01.05.2016, p. 85-92.

研究成果: 雜誌貢獻文章

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title = "ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes",
abstract = "Background ZFHX3 plays an important role in the genesis of atrial fibrillation. However, the atrial electrophysiological effects of ZFHX3 are not clear. This study sought to investigate roles of ZFHX3 in atrial electrophysiology and calcium homeostasis by using HL-1 atrial myocytes knocked-down with ZFHX3. Methods Patch clamp, confocal fluorescence microscopy and Western blot were used to study electrical activity, ionic currents, calcium homeostasis and protein expressions in stable ZFHX3 shRNA cells. Results As compared to control, ZFHX3 shRNA cells with 28{\%} decline of ZFHX3 protein had a larger sarcoplasmic reticulum Ca2+ content by 62{\%}, Ca2+ transient by 20{\%}, and calcium leak by 75{\%}. ZFHX3 shRNA cells (n = 35) had shorter action potential duration (APD) at 50{\%} (14.7 ± 0.9 versus 20.3 ± 1.4 ms, P <0.005), and 20{\%} (6.1 ± 0.3 versus 8.3 ± 0.8 ms, P <0.005) repolarization than control cells (n = 30). ZFHX3 shRNA cells (n = 10) had larger amplitudes of isoproterenol (1 μM)-induced delayed afterdepolarization (14.1 ± 0.9 versus 7.2 ± 0.2 mV, P <0.05) than control cells (n = 10). Besides, acetylcholine (3 μM) shortened APD at 90{\%} repolarization to a greater extent (19 ± 4{\%} versus 7 ± 2{\%}, P <0.01) in ZFHX3 shRNA cells (n = 11) than in control cells (n = 12). In addition, ZFHX3 shRNA cells had increased expressions of SERCA2a, ryanodine receptor, Kv1.4, Kv1.5 and Kir3.4. Moreover, ZFHX3 shRNA cells had a larger SERCA2a activity, ultra-rapid delayed rectifier potassium currents, transient outward currents and acetylcholine-sensitive potassium currents. Conclusions ZFHX3 knock-down in atrial myocytes dysregulated calcium homeostasis and increased atrial arrhythmogenesis, which may contribute to the occurrence of AF.",
keywords = "Atrial arrhythmogenesis, Calcium homeostasis, ZFHX3",
author = "Kao, {Yu Hsun} and Hsu, {Jung Chieh} and Chen, {Yao Chang} and Lin, {Yung Kuo} and Baigalmaa Lkhagva and Chen, {Shih Ann} and Chen, {Yi Jen}",
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T1 - ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes

AU - Kao, Yu Hsun

AU - Hsu, Jung Chieh

AU - Chen, Yao Chang

AU - Lin, Yung Kuo

AU - Lkhagva, Baigalmaa

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background ZFHX3 plays an important role in the genesis of atrial fibrillation. However, the atrial electrophysiological effects of ZFHX3 are not clear. This study sought to investigate roles of ZFHX3 in atrial electrophysiology and calcium homeostasis by using HL-1 atrial myocytes knocked-down with ZFHX3. Methods Patch clamp, confocal fluorescence microscopy and Western blot were used to study electrical activity, ionic currents, calcium homeostasis and protein expressions in stable ZFHX3 shRNA cells. Results As compared to control, ZFHX3 shRNA cells with 28% decline of ZFHX3 protein had a larger sarcoplasmic reticulum Ca2+ content by 62%, Ca2+ transient by 20%, and calcium leak by 75%. ZFHX3 shRNA cells (n = 35) had shorter action potential duration (APD) at 50% (14.7 ± 0.9 versus 20.3 ± 1.4 ms, P <0.005), and 20% (6.1 ± 0.3 versus 8.3 ± 0.8 ms, P <0.005) repolarization than control cells (n = 30). ZFHX3 shRNA cells (n = 10) had larger amplitudes of isoproterenol (1 μM)-induced delayed afterdepolarization (14.1 ± 0.9 versus 7.2 ± 0.2 mV, P <0.05) than control cells (n = 10). Besides, acetylcholine (3 μM) shortened APD at 90% repolarization to a greater extent (19 ± 4% versus 7 ± 2%, P <0.01) in ZFHX3 shRNA cells (n = 11) than in control cells (n = 12). In addition, ZFHX3 shRNA cells had increased expressions of SERCA2a, ryanodine receptor, Kv1.4, Kv1.5 and Kir3.4. Moreover, ZFHX3 shRNA cells had a larger SERCA2a activity, ultra-rapid delayed rectifier potassium currents, transient outward currents and acetylcholine-sensitive potassium currents. Conclusions ZFHX3 knock-down in atrial myocytes dysregulated calcium homeostasis and increased atrial arrhythmogenesis, which may contribute to the occurrence of AF.

AB - Background ZFHX3 plays an important role in the genesis of atrial fibrillation. However, the atrial electrophysiological effects of ZFHX3 are not clear. This study sought to investigate roles of ZFHX3 in atrial electrophysiology and calcium homeostasis by using HL-1 atrial myocytes knocked-down with ZFHX3. Methods Patch clamp, confocal fluorescence microscopy and Western blot were used to study electrical activity, ionic currents, calcium homeostasis and protein expressions in stable ZFHX3 shRNA cells. Results As compared to control, ZFHX3 shRNA cells with 28% decline of ZFHX3 protein had a larger sarcoplasmic reticulum Ca2+ content by 62%, Ca2+ transient by 20%, and calcium leak by 75%. ZFHX3 shRNA cells (n = 35) had shorter action potential duration (APD) at 50% (14.7 ± 0.9 versus 20.3 ± 1.4 ms, P <0.005), and 20% (6.1 ± 0.3 versus 8.3 ± 0.8 ms, P <0.005) repolarization than control cells (n = 30). ZFHX3 shRNA cells (n = 10) had larger amplitudes of isoproterenol (1 μM)-induced delayed afterdepolarization (14.1 ± 0.9 versus 7.2 ± 0.2 mV, P <0.05) than control cells (n = 10). Besides, acetylcholine (3 μM) shortened APD at 90% repolarization to a greater extent (19 ± 4% versus 7 ± 2%, P <0.01) in ZFHX3 shRNA cells (n = 11) than in control cells (n = 12). In addition, ZFHX3 shRNA cells had increased expressions of SERCA2a, ryanodine receptor, Kv1.4, Kv1.5 and Kir3.4. Moreover, ZFHX3 shRNA cells had a larger SERCA2a activity, ultra-rapid delayed rectifier potassium currents, transient outward currents and acetylcholine-sensitive potassium currents. Conclusions ZFHX3 knock-down in atrial myocytes dysregulated calcium homeostasis and increased atrial arrhythmogenesis, which may contribute to the occurrence of AF.

KW - Atrial arrhythmogenesis

KW - Calcium homeostasis

KW - ZFHX3

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