Involvement of Src kinase in the down-regulation of ultra-rapid delayed rectifier K(+)current induced by tumor necrosis factor-α in cardiomyocytes.
10.3760/cma.j.cn112148-20190517-00267
- VernacularTitle:Src激酶参与肿瘤坏死因子α诱导的心房肌细胞超快速延迟整流钾电流下调
- Author:
Hui Shan ZHOU
1
,
2
;
Zhao Yu WANG
3
;
Xiao Yan GAO
4
;
Chun Yu DENG
3
;
Yu Mei XUE
4
;
Hui YANG
3
;
Xin LI
4
;
Su Juan KUANG
3
;
De Wei PENG
3
;
Fang RAO
3
;
Shu Lin WU
5
Author Information
1. School of Medicine, South China University of Technology, Guangdong 510006, China
2. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong 510080, China.
3. Research Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong 510080, China.
4. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong 510080, China.
5. School of Medicine, South China University of Technology, Guangdong 510006, China.
- Publication Type:Journal Article
- Keywords:
Atrial fibrillation;
Atrium myocytes;
I(kur);
Src kinase;
Tumor necrosis factor-alpha
- MeSH:
Animals;
Down-Regulation;
Heart Atria;
Myocytes, Cardiac;
Rats;
Tumor Necrosis Factor-alpha;
src-Family Kinases
- From:
Chinese Journal of Cardiology
2020;48(4):323-328
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 μmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.
