Transmural heterogeneity of repolarization and Ca2+ handling in a model of mouse ventricular tissue
Transmural heterogeneity of repolarization and Ca2+ handling in a model of mouse ventricular tissue
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DOI：
10.1152/ajpheart.00907.2009
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发表时间：
2010-08-01
影响因子：
4.8
通讯作者：
Rasmusson, Randall L.
中科院分区：
文献类型：
--
作者：
Bondarenko, Vladimir E.;Rasmusson, Randall L.
Bondarenko VE，Rasmusson RL.小鼠心室组织模型中复极和钙离子处理的跨壁异质性。Am J Physiol心脏圈Physiol 299：H454-H469,2010。2010年6月4日首次出版；doi：10.1152/ajpheart.00907.2009。-小鼠心脏具有来自不同区域的心肌细胞产生的不同动作电位(AP)。最近的证据表明，来自小鼠心室心外膜和心内膜区域的细胞具有不同的钙处理特性和K+电流表达。为了研究AP在跨壁异质组织中的产生、繁殖和稳定性的机制，我们从心脏的心外膜和心内膜区域建立了一个全面的小鼠心肌细胞模型。我们的计算机模型模拟了心外膜和心内膜心肌细胞之间的以下差异：1)心内膜AP持续时间较长，而心外膜肌细胞AP持续时间较短；2)起搏后心内膜细胞内舒张期和收缩期细胞内钙离子浓度瞬变较高，而心外膜肌细胞内钙离子浓度瞬变较低；3)心内膜细胞钙释放速率约为心外膜心肌细胞的两倍；4)心外膜细胞的Na+/Ca~(2+)交换速率大于心内膜心肌细胞。分离的心外膜细胞表现出更高的AP产生稳定性阈值，但在快速起搏时AP持续时间的模式更复杂。AP在二维组织模型中的传播速度与实验测量结果接近。模拟结果表明，复极化和钙离子处理的异质性在小鼠的整个室壁中持续存在。二维模型中AP传播的稳定性分析表明，在快起搏速度下，AP产生了钙交替和更复杂的跨壁异质不规则复极结构和细胞内钙瞬变。
Bondarenko VE, Rasmusson RL. Transmural heterogeneity of repolarization and Ca2+ handling in a model of mouse ventricular tissue. Am J Physiol Heart Circ Physiol 299: H454-H469, 2010. First published June 4, 2010; doi:10.1152/ajpheart.00907.2009.-Mouse hearts have a diversity of action potentials (APs) generated by the cardiac myocytes from different regions. Recent evidence shows that cells from the epicardial and endocardial regions of the mouse ventricle have a diversity in Ca2+ handling properties as well as K+ current expression. To examine the mechanisms of AP generation, propagation, and stability in transmurally heterogeneous tissue, we developed a comprehensive model of the mouse cardiac cells from the epicardial and endocardial regions of the heart. Our computer model simulates the following differences between epicardial and endocardial myocytes: 1) AP duration is longer in endocardial and shorter in epicardial myocytes, 2) diastolic and systolic intracellular Ca2+ concentration and intracellular Ca2+ concentration transients are higher in paced endocardial and lower in epicardial myocytes, 3) Ca2+ release rate is about two times larger in endocardial than in epicardial myocytes, and 4) Na+/Ca2+ exchanger rate is greater in epicardial than in endocardial myocytes. Isolated epicardial cells showed a higher threshold for stability of AP generation but more complex patterns of AP duration at fast pacing rates. AP propagation velocities in the model of two-dimensional tissue are close to those measured experimentally. Simulations show that heterogeneity of repolarization and Ca2+ handling are sustained across the mouse ventricular wall. Stability analysis of AP propagation in the two-dimensional model showed the generation of Ca2+ alternans and more complex transmurally heterogeneous irregular structures of repolarization and intracellular Ca2+ transients at fast pacing rates.