A mathematical model of the slow force response to stretch in rat ventricular myocytes
A mathematical model of the slow force response to stretch in rat ventricular myocytes
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DOI：
10.1529/biophysj.106.095463
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Smith, Nicolas P.
中科院分区：
文献类型：
--
作者：
Niederer, Steven A.;Smith, Nicolas P.
我们建立了一个室温下的大鼠心室肌细胞模型，以预测不同机制对肌肉长度阶跃变化导致的力量缓慢增加的相对影响。我们模拟了拉伸依赖性增加通过Na+-H+交换器(NHE)和Cl--HCO3-交换器(AE)、拉伸激活通道(SAC)和拉伸依赖的一氧化氮(NO)诱导的兰尼定受体开放概率增加的情况，以估计每种机制产生慢性力反应(SFR)的能力。包括拉伸依赖的NHE&AE、SACS和拉伸依赖的NO效应可使拉伸15分钟后的张力分别增加0.87%、32%和0%。比较拉伸前后的[Ca~(2+)](I)动态变化，发现拉伸依赖的NO效应产生了[Ca~(2+)](I)瞬变，这与实验结果不一致。进一步的模拟表明，在SACS的存在和不存在拉伸依赖的NHE和AE的情况下，抑制NHE可以减弱SFR，因此在NHE阻滞剂的存在下SFR的降低并不表明NHE的拉伸依赖。相反，正常运作的NHE负责SFR的一部分。基于我们的模拟，我们估计，在室温下的大鼠心肌细胞中，囊在产生SFR方面发挥着重要作用，可能是在拉伸依赖的NHE和AE存在的情况下，如果有的话，任何影响都必须涉及更多的机制，而不仅仅是增加ryanodine受体的开放概率。
We developed a model of the rat ventricular myocyte at room temperature to predict the relative effects of different mechanisms on the cause of the slow increase in force in response to a step change in muscle length. We performed simulations in the presence of stretch-dependent increases influx through the Na+-H+ exchanger (NHE) and Cl--HCO3- exchanger (AE), stretch-activated channels (SAC), and the stretch-dependent nitric oxide (NO) induced increased open probability of the ryanodine receptors to estimate the capacity of each mechanism to produce the slow force response (SFR). Inclusion of stretch-dependent NHE & AE, SACs, and stretch-dependent NO effects caused an increase in tension following 15 min of stretch of 0.87%, 32%, and 0%, respectively. Comparing [Ca2+](i) dynamics before and after stretch in the presence of combinations of the three stretch-dependent elements, which produced significant SFR values (>20%), showed that the inclusion of stretch-dependent NO effects produced [Ca2+](i) transients, which were not consistent with experimental results. Further simulations showed that in the presence of SACs and the absence of stretch-dependent NHE & AE inhibition of NHE attenuated the SFR, such that reduced SFR in the presence of NHE blockers does not indicate a stretch dependence of NHE. Rather, a functioning NHE is responsible for a portion of the SFR. Based on our simulations we estimate that in rat cardiac myocytes at room temperature SACs play a significant role in producing the SFR, potentially in the presence of stretch-dependent NHE & AE and that NO effects, if any, must involve more mechanisms than just increasing the open probability of ryanodine receptors.