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Aim To investigate the role of mechano- sensitive ion channel Piezol in regulating electrical re-modeling of atrial myocytes induced by hypertension and to further explore the potential mechanisms.Methods Spontaneously hypertensive rats ( SHR ) aged 30 - 32 weeks treated with or without valsartan (30 mg • kg 1 • d 1 ) were used.Wistar rats were used as control.Western blot was used to detect the protein expression of Piezol , Src and Cavl.2 in atrial appendages of rats and in atrial myocytes ( HL-1 cells) exposed to different levels of high hydrostatic pressure (20 and 40 mmHg) , Piezol inhibitor (GsmTx4) and agonist ( Yodal ) in vitro.Whole-cell patch clamp technique was employed to detect L-tvpe calcium current (ICa, ) and action potential duration ( APD) of atrial myocytes.Results Compared with Wistar rats in control group, the protein expressions of Piezol and Src significantly increased and the expression of Cavl.2 decreased in SHR group (P < 0.05 ), while the a- bove changes could he reversed in SHR treated with valsartan( P < 0.05 ) .Meanwhile, higher hydrostatic pressure (40 mniHg) could increase the expressions of Piezol and Src in HL-1 cells( P <0.05) and decrease the protein expression of Cavl.2 (P <0.05 ) , accompanied by a shortened APD and a decreased ICa,.GsmTx4 could significantly reverse the above changes.In addition, Piezol agonist Yodal could simulate electrical remodeling and related signal molecule changes in atrial myocytes induced by the high hydrostatic pressure.Conclusions Mechanosensitive ion channel Piezol participates in electrical remodeling induced by hypertension via activating Src kinase signaling pathway and then leading to the decrease of ICa ,.
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Aim To observe the effects of sacubitril/valsartan (Sac/Val, LCZ696) on atrial remodeling and atrial fibrillation (AF) susceptibility in spontaneously hypertensive rats (SHR). Methods Twenty-four 7-week-old male SHR were randomly divided into SHR group, SHR + Val group (30 mg · kg
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Aim To explore the role of cotranscriptional activator p300 in regulating the electrical remodeling of atrial myocytes in aging mouse, which resulted in atrial fibrillation. Methods The left atrial appendage tissues of 5 , 13 and 18monthold C57BL/6 mice were collected respectively. Western blot was used to detect the protein expression levels of p300, L type calcium channel (Cavl. 2) and aging related protein p53/p21. Acute enzymatic hydrolysis was used to isolate single atrial myocytes, and the wholecell patchclamp technique was used to detect the Ltype calcium current (I
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.