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外界刺激对钠通道基因突变的窦房结体系起搏功能的调控作用

, PP. 657-662

Keywords: 基因突变,计算机模拟,钠通道,异常起搏,二维窦房结模型

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Abstract:

采用完整的二维兔子窦房结-心房细胞模型,考虑2种类型钠离子基因突变的影响,如功能缺失型突变、功能获得型突变,本研究考察了包括迷走神经分泌的乙酰胆碱、酸性浓度和组织温度3种外界刺激对心脏起搏和传导能力的调控作用.研究结果表明,这2种类型的基因突变对起搏速率、传导能力有不同的影响.本研究还发现,这些突变的消极作用可通过3种外界刺激进行调节:增加乙酰胆碱浓度可增强突变诱导窦房结心搏徐缓的效果;改变酸浓度或调节组织温度可以有效地增强窦房结驱动周围心房组织及恢复组织起搏行为的能力.上述研究将有助于揭示钠离子通道疾病的内在机制,并有望提供一些可能的治疗手段.

References

[1]  23 Pakhcmov A G, Mathur S P, Doyle J, et al. Comparative effects of extremely high power microwave pulses and brief CW irradiation on pacemaker function in isolated frog heart slices. Bioelectromagnetics, 2000, 110: 351-360
[2]  24 Tei C, Horikiri Y, Park J C, et al. Acute hemodynamic improvement by thermal vasodilation in congestive heart failure. Circulation, 1995, 91: 2582-2590
[3]  25 Boone T, Westendorf T, Ayres P, Cardiovascular responses to a hot tub bath. J Altern Complem Med, 1999, 5: 301-304
[4]  26 Rosenbaum T, Gordon S E. Quickening the pace: looking into the heart of HCN channels. Neuron, 2004, 42: 193-196
[5]  1 Heribert S, Konig I R, Sekar K, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genet, 2011, 43: 333-338
[6]  2 杨银峰,朱月春,李丹怡, 等. 中国西南阿昌族G6PD缺陷的特征及新单体型487G>A/IVS5-612(G>C)的鉴定. 中国科学C辑: 生命科学, 2007, 37: 460-465
[7]  3 Herfst L J, Book M B, Jongsma H J. Trafficking and functional expression of cardiac Na+ channels. J Mod Cell Cardiol, 2004, 36: 185-193
[8]  4 Shimizu W, Aiba T, Kamakura S. Mechanisms of disease: current understanding and future challenges in Brugada syndrome. Nat Clin Pract Cardiovasc Med, 2005, 2: 408-414
[9]  5 Juang J M, Huang S K. Brugada syndrome-an under-recognized electrical disease in patients with sudden cardiac death. Cardiology, 2004, 101: 157-169
[10]  6 Vatta M, Dumaine R, Varghese G, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet, 2002, 11: 337-345
[11]  7 Benson D W, Wang D W, Dyment M, et al. Congenital sick sinus syndrome caused by recessicve mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest, 2003, 112: 1019-1028
[12]  8 Dobrzynski H, Boyeet M R, Anderson R H. Newo insights into pacemaker activity: Promoting understanding of sick sinus syndrome. Circulation, 2007, 115: 1921-1932
[13]  9 Schott J J, Alshinawi C, Kyndt F, et al. Cardiac conduction defects associated with mutations in SCN5A. Nature Genet, 1999, 23: 20-21
[14]  10 Chiang C E. Congenital and acquired long QT syndrome: current concepts and management. Cardiol Rev, 2004, 12: 222-234
[15]  11 Towbin J A, Vatta M. Molecular biology and the prolonged QT syndromes. Am J Med, 2001, 110: 385-398
[16]  12 Ackerman M J, Siu B L, Sturner W Q, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA, 2001, 286: 2264-2269
[17]  13 Plant L D, Bowers P N, Liu Q, et al. A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. J Clin Invest, 2006, 116: 430-435
[18]  14 Viswanathan P C, Balser J R. Inherited sodium channelopathies: a continuum of channel dysfunction. Trends Cardiovasc Med, 2004, 14: 28-35
[19]  15 Chen H S, Zhang J Q, Liu J Q. Selective effects of external noise on Ca2+ signal in mesoscopic scale biochemical cell systems. Biophys Chem, 2007, 125: 397-402
[20]  16 Zhang J Q, Qi F, Xin H W. Effects of noise on the off rate of Ca2+ binding proteins in a coupled biochemical cell system. Biophys Chem, 2001, 94: 201-207
[21]  17 Zhang H, Holden A V, Kodama I, et al. Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node. Am J Physiol Heart Circ Physiol, 2000, 279: 397-421
[22]  18 Zhang H, Zhao Y, Lei M, et al. Computational evaluation of the roles of Na+ current, iNa, and cell death in cardiac pacemaking and driving. Am J Physiol Heart Circ Physiol, 2007, 292: 165-174
[23]  19 Timothy D B, Oleg VA, Shin I, et al. Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome. Circ. Res, 2010, 107: 126-137
[24]  20 Honjo H, Boyett M R, Kodama I, et al. Correlation between electrical activity and the size of rabbit sinoatrial node cells. J Physiol, 1996, 496: 795-808
[25]  21 Wani B A, Khalil M Z, Al-Nozha M M, et al. Aborted sudden nocturnal cardiac death in a young man with structurally normal heart. Saudi Med J, 2005, 26: 323-325
[26]  22 Brian P D, Jonathan S. pH modification of human T-type calcium channel gating. Biophys J, 2000, 78: 1895-1905

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