A dynamic model of excitation-contraction coupling during acidosis in cardiac ventricular myocytes
A dynamic model of excitation-contraction coupling during acidosis in cardiac ventricular myocytes
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DOI：
10.1529/biophysj.105.070557
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Smith, NP
中科院分区：
文献类型：
--
作者：
Crampin, EJ;Smith, NP
心肌细胞的酸中毒是缺血心脏收缩力降低的主要因素。在酸中毒期间，舒张期钙浓度和钙瞬变幅度增加，而收缩强度降低。这归因于质子对肌浆网钙摄取和释放的抑制，归因于钠-氢交换激活引起的细胞内钠升高，钙与肌钙蛋白-C的结合亲和力降低，以及对收缩机制的直接影响。然而，这些效应的相对贡献和协同作用很难通过实验确定。我们已经开发了一个数学模型来检查改变钙处理机制在酸中毒。每一个改变被纳入到一个动态模型的pH值调节和兴奋收缩耦合预测的时间过程中的关键离子种类酸中毒，特别是细胞内的pH值，钠和钙瞬变，和收缩。这项建模研究表明，最显着的影响是钠升高，抑制钠钙交换，质子与收缩机械的直接相互作用;并显示了如何协调这些贡献的实验数据，以了解跳动的心脏酸中毒的整体影响。
Acidosis in cardiac myocytes is a major factor in the reduced inotropy that occurs in the ischemic heart. During acidosis, diastolic calcium concentration and the amplitude of the calcium transient increase, while the strength of contraction decreases. This has been attributed to the inhibition by protons of calcium uptake and release by the sarcoplasmic reticulum, to a rise of intracellular sodium caused by activation of sodium-hydrogen exchange, decreased calcium binding affinity to Troponin-C, and direct effects on the contractile machinery. The relative contributions and concerted action of these effects are, however, difficult to establish experimentally. We have developed a mathematical model to examine altered calcium-handling mechanisms during acidosis. Each of the alterations was incorporated into a dynamical model of pH regulation and excitation-contraction coupling to predict the time courses of key ionic species during acidosis, in particular intracellular pH, sodium and the calcium transient, and contraction. This modeling study suggests that the most significant effects are elevated sodium, inhibition of sodium-calcium exchange, and the direct interaction of protons with the contractile machinery; and shows how the experimental data on these contributions can be reconciled to understand the overall effects of acidosis in the beating heart.