Differential expression of BKCa channels in atrial fibroblasts in patients with sinus rhythm and atrial fibrillation_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

BI Hongqin ¹ , LI Miaoling ² , ZHOU Wei ¹ , LI Guang ² , DONG Yahui ¹ , HUANG Tao ¹ ,  YU Fengxu ¹

1. Department of Cardiothoracic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, P.R.China;
2. The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Southwest Medical University, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Luzhou, 646000, Sichuan, P.R.China;

Corresponding author：

YU Fengxu, Email: yuluchuan@163.com

Keywords：

Atrial fibrillation; sinus rhythm; fibroblasts; BKCa

DOI：

10.7507/1007-4848.201707042

Video：

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Objective Through analyzing BKCa channel expression in atrial fibroblasts in patients with sinus rhythm and atrial fibrillation (AF), to explore the mechanism of myocardial fibrosis and provide new therapeutic strategies for the treatment and reversal of AF structure reconstruction. Methods We selected 10 patients of rheumatic heart valvular disease who underwent valve replacement surgery. They were 5 patients with sinus rhythm (a sinus rhythm group, 2 males and 3 females with an average age of 49.1±8.3 years) and 5 with AF (an AF group, 3 males and 2 females with an average age of 50.3±5.8 years). About 100 mg tissue was obtained from the right auricula dextra, and the atrial fibroblasts were cultured by tissue block adherence method, and the expression of BKCa channel genes and proteins in cultured fibroblasts was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting methods. Results (1) The general data of 10 patients between the AF group and the sinus rhythm group were compared. There was no significant difference between the two groups in age (t=1.21, P=0.67) and sex (t=2.56, P=0.75). There was statistical difference in the left atrial diameter and the right atrium diameter between the two groups (t=19.45, P=0.01; t=23.52, P=0.06); (2) the mRNA expression of BKCa subunit was detected by qRT-PCR method, and there was no significant difference in the mRNA expression of BKCa α and BKCa β1 between the two groups (t=3.14, P=0.79; t=2.88, P=0.69); (3) the expression of BKCa protein was detected by western blotting method, and there was no significant difference in the protein expression of BKCa α and BKCa β1 between the two groups (t=0.55, P=0.31; t=0.73, P=0.46). Conclusion BKCa pathway may not be involved in the pathogenesis and maintenance of AF, but it may play an important role in the process of myocardial fibrosis.

Citation： BI Hongqin, LI Miaoling, ZHOU Wei, LI Guang, DONG Yahui, HUANG Tao, YU Fengxu. Differential expression of BKCa channels in atrial fibroblasts in patients with sinus rhythm and atrial fibrillation. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(12): 937-942. doi: 10.7507/1007-4848.201707042 Copy

1.	Nattel S, Li D, Yue L. Basic mechanisms of atrial fibrillation--very new insights into very old ideas. Annu Rev Physiol, 2000, 62: 51-77.
2.	Moe GW, Laurent G, Doumanovskaia L, et al. Matrix metalloproteinase inhibition attenuates atrial remodeling and vulnerability to atrial fibrillation in a canine model of heart failure. J Card Fail, 2008, 14(9): 768-776.
3.	Greiser M, Neuberger HR, Harks E, et al. Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation. J Mol Cell Cardiol, 2009, 46(3): 385-394.
4.	Thijssen VL, Ausma J, Liu GS, et al. Structural changes of atrial myocardium during chronic atrial fibrillation. Cardiovasc Pathol, 2000, 9(1): 17-28.
5.	Thijssen VL, van der Velden HM, van Ankeren EP, et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res, 2002, 54(2): 427-37.
6.	Tan A Y, Zimetbaum P. Atrial fibrillation and atrial fibrosis. J Cardiovasc Pharm, 2011, 57(6): 625-629.
7.	Kostin S, Klein G, Szalay Z, et al. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res, 2002, 54(2): 361-79.
8.	Yang Y, Li PY, Cheng J, et al. Function of BKCa channels is reduced in human vascular smooth muscle cells from Han Chinese patients with hypertension. Hypertension, 2013, 61(2): 519-25.
9.	Wang YJ, Sung RJ, Lin MW, et al. Contribution of BK(Ca)-channel activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts. J Membr Biol, 2006, 213(3): 175-185.
10.	Sheng J, Shim W, Wei H, et al. Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts. J Cell Mol Med, 2013, 17(10): 1345-54.
11.	Cruse G, Singh SR, Duffy SM, et al. Functional KCa3.1 K+ channels are required for human fibrocyte migration. J Allergy Clin Immunol, 2011, 128(6): 1303-1309.e2.
12.	Meera P, Wallner M, Song M, et al. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc Natl Acad Sci USA, 1997, 94(25): 14066-14071.
13.	张建成, 程显禄, 黄宇坚, 等. 采用组织块法培养心房纤颤动患者心房成纤维细胞. 中国心脏起搏与心电生理杂志, 2009, 23(6): 506-508.
14.	Han ZM, Chen DY, Li JS, et al. Flow cytometric cell-cycle analysis of cultured fibroblasts from the giant panda, Ailuropoda melanoleuca L. Cell Biol Int, 2003, 27(4): 349-353.
15.	Lyle S, Christofidou-Solomidou M, Liu Y, et al. Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype. J Investig Dermatol Symp Proc, 1999, 4(3): 296-301.
16.	Balderas E, Zhang J, Stefani E, et al. Mitochondrial BKCa channel. Front Physiol, 2015, 6: 104.
17.	Miragoli M, Gaudesius G, Rohr S. Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res, 2006, 98(6): 801-810.
18.	Wang J, Chen H, Seth A, et al. Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts. Am J Physiol Heart Circ Physiol, 2003, 285(5): H1871-H1881.
19.	Miragoli M, Salvarani N, Rohr S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res, 2007, 101(8): 755-758.

1. Nattel S, Li D, Yue L. Basic mechanisms of atrial fibrillation--very new insights into very old ideas. Annu Rev Physiol, 2000, 62: 51-77.
2. Moe GW, Laurent G, Doumanovskaia L, et al. Matrix metalloproteinase inhibition attenuates atrial remodeling and vulnerability to atrial fibrillation in a canine model of heart failure. J Card Fail, 2008, 14(9): 768-776.
3. Greiser M, Neuberger HR, Harks E, et al. Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation. J Mol Cell Cardiol, 2009, 46(3): 385-394.
4. Thijssen VL, Ausma J, Liu GS, et al. Structural changes of atrial myocardium during chronic atrial fibrillation. Cardiovasc Pathol, 2000, 9(1): 17-28.
5. Thijssen VL, van der Velden HM, van Ankeren EP, et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res, 2002, 54(2): 427-37.
6. Tan A Y, Zimetbaum P. Atrial fibrillation and atrial fibrosis. J Cardiovasc Pharm, 2011, 57(6): 625-629.
7. Kostin S, Klein G, Szalay Z, et al. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res, 2002, 54(2): 361-79.
8. Yang Y, Li PY, Cheng J, et al. Function of BKCa channels is reduced in human vascular smooth muscle cells from Han Chinese patients with hypertension. Hypertension, 2013, 61(2): 519-25.
9. Wang YJ, Sung RJ, Lin MW, et al. Contribution of BK(Ca)-channel activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts. J Membr Biol, 2006, 213(3): 175-185.
10. Sheng J, Shim W, Wei H, et al. Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts. J Cell Mol Med, 2013, 17(10): 1345-54.
11. Cruse G, Singh SR, Duffy SM, et al. Functional KCa3.1 K+ channels are required for human fibrocyte migration. J Allergy Clin Immunol, 2011, 128(6): 1303-1309.e2.
12. Meera P, Wallner M, Song M, et al. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc Natl Acad Sci USA, 1997, 94(25): 14066-14071.
13. 张建成, 程显禄, 黄宇坚, 等. 采用组织块法培养心房纤颤动患者心房成纤维细胞. 中国心脏起搏与心电生理杂志, 2009, 23(6): 506-508.
14. Han ZM, Chen DY, Li JS, et al. Flow cytometric cell-cycle analysis of cultured fibroblasts from the giant panda, Ailuropoda melanoleuca L. Cell Biol Int, 2003, 27(4): 349-353.
15. Lyle S, Christofidou-Solomidou M, Liu Y, et al. Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype. J Investig Dermatol Symp Proc, 1999, 4(3): 296-301.
16. Balderas E, Zhang J, Stefani E, et al. Mitochondrial BKCa channel. Front Physiol, 2015, 6: 104.
17. Miragoli M, Gaudesius G, Rohr S. Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res, 2006, 98(6): 801-810.
18. Wang J, Chen H, Seth A, et al. Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts. Am J Physiol Heart Circ Physiol, 2003, 285(5): H1871-H1881.
19. Miragoli M, Salvarani N, Rohr S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res, 2007, 101(8): 755-758.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Differential expression of BKCa channels in atrial fibroblasts in patients with sinus rhythm and atrial fibrillation

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