Model of Excitation-Contraction Coupling of Rat Neonatal Ventricular Myocytes
Model of Excitation-Contraction Coupling of Rat Neonatal Ventricular Myocytes
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DOI：
10.1016/j.bpj.2008.10.026
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发表时间：
2009-02-04
影响因子：
3.4
通讯作者：
Tavi, Pasi
中科院分区：
文献类型：
--
作者：
Korhonen, Topi;Hanninen, Sandra L.;Tavi, Pasi
新生大鼠心室肌细胞培养是最常用的实验性心肌细胞模型之一。据我们所知，这些细胞的兴奋-收缩偶联（ECC），即，将电活动与胞质Ca 2+瞬变和收缩联系起来的过程以前没有被分析过，也没有详细地作为一个完整的系统提出。新生心肌细胞处于出生后的发育阶段，因此，其ECC的特征与成人心室肌细胞的特征有很大不同。我们提出了第一个完整的分析ECC在这些细胞的实验特征的动作电位和钙信号，并开发了第一个数学模型ECC在新生儿心肌细胞，我们知道。我们发现，在比较成年心肌细胞，新生心肌细胞有长的动作电位，异质性胞浆钙信号，较弱的肌浆网钙处理，和较强的肌膜钙处理，与Na+/Ca 2+交换的显着贡献。开发的模型忠实地再现ECC的大鼠新生心肌细胞的空间胞浆[Ca 2 +]信号的一种新的描述。模拟还展示了细胞大小的增加（肥大）如何影响新生心肌细胞的ECC。这种发育心肌细胞的ECC模型为开发不同发育阶段的心肌细胞的未来模型提供了平台。
The neonatal rat ventricular myocyte culture is one of the most popular experimental cardiac cell models. To our knowledge, the excitation-contraction coupling (ECC) of these cells, i.e., the process linking the electrical activity to the cytosolic Ca2+ transient and contraction, has not been previously analyzed, nor has it been presented as a complete system in detail. Neonatal cardiomyocytes are in the postnatal developmental stage, and therefore, the features of their ECC differ vastly from those of adult ventricular myocytes. We present the first complete analysis of ECC in these cells by characterizing experimentally the action potential and calcium signaling and developing the first mathematical model of ECC in neonatal cardiomyocytes that we know of. We show that in comparison to adult cardiomyocytes, neonatal cardiomyocytes have long action potentials, heterogeneous cytosolic Ca2+ signals, weaker sarcoplasmic reticulum Ca2+ handling, and stronger sarcolemmal Ca2+ handling, with a significant contribution by the Na+/Ca2+ exchanger. The developed model reproduces faithfully the ECC of rat neonatal cardiomyocytes with a novel description of spatial cytosolic [Ca2+] signals. Simulations also demonstrate how an increase in the cell size (hypertrophy) affects the ECC in neonatal cardiomyocytes. This model of ECC in developing cardiomyocytes provides a platform for developing future models of cardiomyocytes at different developmental stages.