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首页> 外文期刊>Journal of Theoretical Biology >Characterization of the cardiac Na+/K+ pump by development of a comprehensive and mechanistic model.
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Characterization of the cardiac Na+/K+ pump by development of a comprehensive and mechanistic model.

机译：通过开发全面的机械模型来表征心脏Na + / K +泵。

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A large amount of experimental data on the characteristics of the cardiac Na(+)/K(+) pump have been accumulated, but it remains difficult to predict the quantitative contribution of the pump in an intact cell because most measurements have been made under non-physiological conditions. To extrapolate the experimental findings to intact cells, we have developed a comprehensive Na(+)/K(+) pump model based on the thermodynamic framework (Smith and Crampin, 2004) of the Post-Albers reaction cycle combined with access channel mechanisms. The new model explains a variety of experimental results for the Na(+)/K(+) pump current (I(NaK)), including the dependency on the concentrations of Na(+) and K(+), the membrane potential and the free energy of ATP hydrolysis. The model demonstrates that both the apparent affinity and the slope of the substrate-I(NaK) relationship measured experimentally are affected by the composition of ions in the extra- and intracellular solutions, indirectly through alteration in the probability distribution of individual enzyme intermediates. By considering the voltage dependence in the Na(+)- and K(+)-binding steps, the experimental voltage-I(NaK) relationship could be reconstructed with application of experimental ionic compositions in the model, and the view of voltage-dependent K(+) binding was supported. Re-evaluation of charge movements accompanying Na(+) and K(+) translocations gave a reasonable number for the site density of the Na(+)/K(+) pump on the membrane. The new model is relevant for simulation of cellular functions under various interventions, such as depression of energy metabolism.
机译：积累了关于心脏Na（+）/ K（+）泵特性的大量实验数据，但由于大多数测量是在非饱和状态下进行的，因此很难预测完整细胞中泵的定量贡献。 -生理条件。为了将实验结果外推至完整细胞，我们基于后阿尔伯斯反应周期的热力学框架（Smith和Crampin，2004）与访问通道机制相结合，开发了一个综合的Na（+）/ K（+）泵模型。新模型解释了Na（+）/ K（+）泵浦电流（I（NaK））的各种实验结果，包括对Na（+）和K（+）浓度，膜电位和ATP水解的自由能。该模型表明，实验测得的表观亲和力和底物-I（NaK）关系的斜率都受到细胞外和细胞内溶液中离子组成的影响，这间接地是通过改变各个酶中间体的概率分布来实现的。通过考虑Na（+）-和K（+）结合步骤中的电压依赖性，可以通过在模型中应用实验离子组成和电压依赖性的观点来重建实验电压-I（NaK）关系。支持K（+）绑定。重新评估伴随Na（+）和K（+）易位的电荷运动为膜上Na（+）/ K（+）泵的位点密度提供了一个合理的数字。该新模型与在各种干预（例如能量代谢抑制）下的细胞功能模拟有关。

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