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Role of tumour necrosis factor‐a in the regulation of T‐type calcium channel current in HL ‐1 cells
Author(s) -
Rao Fang,
Xue Yumei,
Wei Wei,
Yang Hui,
Liu Fangzhou,
Chen Shaoxian,
Kuang Sujuan,
Zhu Jiening,
Wu Shulin,
Deng Chunyu
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12585
Subject(s) - pathogenesis , tumor necrosis factor alpha , endocrinology , medicine , chemistry , myocyte , inflammation , calcium channel , necrosis , l type calcium channel , calcium
Summary Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation ( AF ). Although tumour necrosis factor ( TNF )‐ α levels are increased in patients with AF , the role of TNF ‐ α in the pathogenesis of AF remains unclear. Besides L‐type Ca 2+ currents ( I Ca,L ), T‐type Ca 2+ currents ( I Ca,T ) also plays an important role in the pathogenesis of AF . This study was designed to use the whole‐cell voltage‐clamp technique and biochemical assays to explore if TNF ‐ α is involved in the pathogenesis of AF through regulating I Ca,T in atrial myocytes. It was found that compared with sinus rhythm ( SR ) controls, T‐type calcium channel ( TCC ) subunit mRNA levels were decreased, while TNF ‐ α expression levels were increased, in human atrial tissue from patients with AF . In murine atrial myocyte HL ‐1 cells, after culturing for 24 h, 12.5, 25 and 50 ng/ mL TNF ‐ α significantly reduced the protein expression levels of the TCC α 1G subunit in a concentration‐dependent manner. The peak current was reduced by the application of 12.5 or 25 ng/ mL TNF ‐ α in a concentration‐dependent manner (from −15.08 ± 1.11 pA / pF in controls to −11.89 ± 0.83 pA / pF and −8.54 ± 1.55 pA / pF in 12.5 or 25 ng/ mL TNF ‐ α group respectively). TNF ‐ α application also inhibited voltage‐dependent inactivation of I Ca,T , shifted the inactivation curve to the left. These results suggest that TNF ‐ α is involved in the pathogenesis of AF , probably via decreasing I Ca,T current density in atrium‐derived myocytes through impaired channel function and down‐regulation of channel protein expression. This pathway thus represents a potential pathogenic mechanism in AF.