血管紧张素Ⅱ2型受体对人房颤心房细胞的影响——对心房肌细胞瞬间外向钾离子通道的作用Effect and Mechanism of Angiotensin Ⅱ Receptor Type 2 on Transient outward K~+ Current Remodeling in Human atrial Myocytes
张文昶,赵长林,郑振达,陈纯波,吴书林
ZHANG Wen-Chang1,ZHAO Chang-Lin1,ZHENG Zhen-Da1,CHEN Chun-Bo2, WU Shu-Lin2 (1.Division of cardiology
摘要(Abstract):
目的研究血管紧张素Ⅱ2型受体(AT2)对单个人心房颤动心房肌细胞瞬间外向钾电流(Ito1)的影响。方法选择择期行心脏体外循环手术的持续性心房颤动(>6个月)患者,建立体外循环前取右心耳组织约0.3cm3,放入氧饱和的4℃心脏停搏液中,5min内送回实验室。用胶原酶Ⅱ两步酶解法分离出单个心房肌细胞,用标准的全细胞膜片钳技术记录瞬间外向钾电流,观察0.5mmol/LCGP42112及0.5mmol/LPD123319引起单个人心房颤动心房肌细胞瞬间外向钾电流(Ito1)改变。结果窦律空白对照组Ito1峰值电流密度为(12.73±7.75)pA/pF(n=7),房颤空白对照组Ito1峰值电流密度为(4.42±1.62)pA/pF(n=8),心房颤动空白对照组Ito1峰值电流密度明显降低(P<0.05)。CGP42112灌流前后窦律组及心房颤动组Ito1峰值电流密度无明显变化(P>0.05);PD123319灌流不影响窦律组及心房颤动组Ito1峰值电流密度(P>0.05)。结论心房颤动患者心房肌细胞Ito1电流密度较窦律患者减少,心房颤动致Ito1通道的电生理特性改变。AT2受体激活和失活均不改变窦律患者和心房颤动患者心房肌细胞Ito1通道电流密度,表明Ito1的下调不完全通过AT2介导。
Objective To determine the effect and mechanism of angiotensin Ⅱ receptor type 2 on Transient outward K+ current remodeling in humans atrial myocytes.Methode Whole-cell pacth-clamp recording technique was used to record Ito1 in humans atrial myocytes.Results The Ito1 was recorded in humans atrial myocytes.The effects of CGP 42112 and PD 123319 on current densities of Ito1.The peak current densities of Ito1 in AF group was lower than those in SR group [(4.42±1.62)pA /pF(n=8)vs(12.73±7.75)pA /pF(n=7),P<0.05]. CGP 42112 had no effect on the peak current densities of Ito1 in SR group (12.99±7.75 pA /pF vs 12.73±7.75 pA /pF,n=7,P>0.05) and in AF group(4.14±0.74 pA /pF vs 4.42±1.62 pA /pF,n=8,P>0.05).PD 123319 had no effect on the peak current densities of Ito1 in SR group (11.83±7.90 pA /pF vs 12.99±7.75 pA /pF,n=7,P>0.05) and in AF group (3.68±0.52 pA /pF vs 4.14±0.74 pA /pF,n=8,P>0.05).Conclusion Selective AT2 agonist and antagonist has no effect on the current densities Ito1 in AF and SR groups.
关键词(KeyWords):
心房颤动;心房肌细胞;血管紧张素Ⅱ2型受体;瞬间外向钾电流;全细胞膜片钳技术
atrial fibrillation;angiotensin II type 2 receptor; transient outward K+ current; humans atrial myocytes; whole-cell patch-clamp.
基金项目(Foundation):
作者(Author):
张文昶,赵长林,郑振达,陈纯波,吴书林
ZHANG Wen-Chang1,ZHAO Chang-Lin1,ZHENG Zhen-Da1,CHEN Chun-Bo2, WU Shu-Lin2 (1.Division of cardiology
参考文献(References):
- 1Wijffels MCEF,Kirchof CJHJ,Dorland RD,et al.Atrial fi-brillation begets atrial fibrillation:a study in awake chroni-cally instrumented goats.Circulation,1995,92(7):1954-1968.
- 2Liu DW,Gintant GA,Antzelevutch C.Ionic bases for electrophysiological distinctions among epicardial,midmyocardi-al,and endocardial myocytes fromthe free wall of the canine left ventricle.Circ Res,1993,72:671-687.
- 3Tieleman RG,Blaauw Y,Van Gelder IC,et al.Digoxin delays recovery from tachycardia-induced electrical remode-ling of the atria.Circulation,1999,100:1836-1842.
- 4陈纯波,吴书林,邓春玉,等。血管紧张素Ⅱ2型受体对人心房肌细胞离子重构的影响。中华心血管病杂志。2005,33(6):550-551
- 5Pedersen OD,Bagger H,Kober L,et al.Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction.Circulation,1999,100:376-380.
- 6Lindholm LH,Dahlof B,Edelman JM,et al.LIFE Study Group.Effect of losartan on sudden cardiac death in people with diabetes:data from the LIFE study.Lancet,2003,362:619-620.
- 7Madrid AH,Bueno MG,Rebollo JM,et al.Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation:a prospective and randomized study.Circulation,2002,106:331-336.
- 8Pappone C,Rosanio S,Augello G,et al.Mortality,morbidity,and quality of life after circumferential pulmona-ry vein ablation for atrial fibrillation:outcomes from a con-trolled non-randomized long-term study.J Am Coll Car-diol,2003,42:185-197.
- 9Dun W,Chandra P,Danilo P Jr,et al.Chronic atrial fibrillation does not further decrease outward currents.It increases them.Am J Physiol Heart Circ Physiol.2003,285(4):1378-1384.
- 10张建成,黄从新,邓玉莲,等.心房颤动患者离子重构的分子基础.中华心律失常学杂志,2002,6(2):84-88.
- 11Petkova-Kirova PS,Gursoy E,Mehdi H,et al.Electri-cal remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.Am J Physiol Heart Circ Physiol.2006,290(5):2098-2107.
- 12Kaab S,Nuss HB,Chiamvimonvat N,et al.Ionic mechanismof action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure.Circ Res.1996,78(2):262-273.
- 13Bernal J,Pitta SR,Thatai D.Role of the renin-angiotensin-aldosterone system in diastolic heart failure:potential for pharmacologic intervention.Am J Cardiovasc Drugs.2006,6(6):373-381.
- 14De Mello WC,Monterrubio J.Intracellular and extracellular angiotensinⅡenhance the L-type calcium current in the failing heart.Hypertension.2004,44(3):360-364.
- 15De Mello WC.Renin increments the inward calcium current in the failing heart.J Hypertens.2006,24(6):1181-1186.
- 16Bosch RF,Scherer CR,Rub N,et al.Molecular mechanisms of early electrical remodeling:transcriptional downregulation of ion channel subunits reduces ICaLand Itolin rapid atrial pacing in rabbits.J Am Coll Cardiol,2003,41:858-869.
- 心房颤动
- 心房肌细胞
- 血管紧张素Ⅱ2型受体
- 瞬间外向钾电流
- 全细胞膜片钳技术
atrial fibrillation - angiotensin II type 2 receptor
- transient outward K+ current
- humans atrial myocytes
- whole-cell patch-clamp.
- 张文昶
- 赵长林
- 郑振达
- 陈纯波
- 吴书林
ZHANG Wen-Chang1 - ZHAO Chang-Lin1
- ZHENG Zhen-Da1
- CHEN Chun-Bo2
- WU Shu-Lin2 (1.Division of cardiology
- 张文昶
- 赵长林
- 郑振达
- 陈纯波
- 吴书林
ZHANG Wen-Chang1 - ZHAO Chang-Lin1
- ZHENG Zhen-Da1
- CHEN Chun-Bo2
- WU Shu-Lin2 (1.Division of cardiology