Schrickel Jan W, Brixius Klara, Herr Claudia, Clemen Christoph S, Sasse Philipp, Reetz Kathrin, Grohé Christian, Meyer Rainer, Tiemann Klaus, Schröder Rolf, Bloch Wilhelm, Nickenig Georg, Fleischmann Bernd K, Noegel Angelika A, Schwinger Robert H G, Lewalter Thorsten
Department of Medicine-Cardiology, University of Bonn, Germany.
Cardiovasc Res. 2007 Nov 1;76(2):257-68. doi: 10.1016/j.cardiores.2007.07.001. Epub 2007 Jul 6.
Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)).
Nineteen adult annexin A7(-/-) and 14 wild-type mice were examined electrophysiologically in vivo by transvenous catheterization. Hearts were additionally perfused by the Langendorff method and epicardial activation mapping was performed.
The susceptibility to induction of atrial fibrillation was elevated in annexin A7(-/-) mice. Ten deficient animals showed atrial fibrillation (AF) episodes > or =1 min and sustained AF > or =30 min was observed in 4 annexin A7(-/-) mice, but in none of the wild-type mice. The incidence of ventricular tachycardia (VT) was higher in annexin A7(-/-) mice and VT duration was prolonged. Epicardial mapping showed elevated anisotropy and inhomogeneity of conduction, leading to conduction blocks in the deficient mice. Besides alterations of intracellular calcium homeostasis, electron microscopy showed a homogeneous, electron-dense material that filled the myocardial intercellular compartments and accumulated at the basement membranes. This led to expansion of the extracellular spaces, which was the most probable substrate factor responsible for the disturbances of electrical communication.
Annexin A7 deficiency causes severe electrical instability in the murine heart, including conduction disturbances and anisotropy of impulse propagation, which is accompanied by disturbed calcium handling and intercellular deposits.
膜联蛋白A7参与心肌细胞膜组织和钙依赖信号传导过程。我们使用膜联蛋白A7基因敲除小鼠品系（膜联蛋白A7(-/-)）研究了膜联蛋白A7对心脏电生理特性的影响。
通过经静脉导管插入术对19只成年膜联蛋白A7(-/-)小鼠和14只野生型小鼠进行体内电生理检查。另外，采用Langendorff方法对心脏进行灌注，并进行心外膜激动标测。
膜联蛋白A7(-/-)小鼠诱发心房颤动的易感性增加。10只基因敲除小鼠出现持续时间≥1分钟的心房颤动（AF）发作，4只膜联蛋白A7(-/-)小鼠出现持续时间≥30分钟的持续性AF，但野生型小鼠均未出现。膜联蛋白A7(-/-)小鼠室性心动过速（VT）的发生率更高，且VT持续时间延长。心外膜标测显示传导的各向异性和不均匀性增加，导致基因敲除小鼠出现传导阻滞。除了细胞内钙稳态改变外，电子显微镜显示一种均匀的、电子致密物质充满心肌细胞间间隙并积聚在基底膜处。这导致细胞外间隙扩大，这很可能是导致电传导紊乱的底物因素。
膜联蛋白A7缺乏导致小鼠心脏严重的电不稳定，包括传导障碍和冲动传播的各向异性，同时伴有钙处理紊乱和细胞间沉积物。
