MODELING OF NA/K PUMP ACTIVITY IN CARDIAC MYOCYTES

Na/K泵是一种重要的膜蛋白， 从生物化学、生理学、生物学和 生物药理学上。 Na/K泵负责维持离子梯度 穿过细胞膜 在心脏中，Na/K泵也很重要 在临床上，对于由以下物质产生的变力和变时作用， Na/K泵活性的药理学或生理学改变。 尽管如此，Na/K泵的详细机制仍然难以捉摸。 本研究的长期目标是了解Na/K泵如何： 1)在生理上调节其活性，对心脏的敏感性， 糖苷和部位危险; 2）在病理生理学上受到调节（例如， 缺血和充血性心力衰竭）;和3）参与 调节心脏的电活动和机械活动。 本研究 将集中在计算机模型的定义和利用， 预测Na/K泵在各种条件下的行为， 尤其是生理和临床相关的病症。 一 这项研究的主要目标是将生物化学信息 钠/钾泵上可用，以帮助生理和生物物理 实验 这项工作将有助于更好地了解Na/K 泵的功能，并应导致新的见解的作用，钠/钾 心脏泵功能。 这项建议将补充正在进行的研究 在这个实验室中，通过将模型中产生的数据 Na/K泵离子依赖性和电压依赖性的实验研究 用全细胞膜片钳技术测量的分离的 肌细胞 本研究将利用这些实验结果，以及 其他实验室发表的结果，构建一个模型， Na/K泵。 该模型将结合已知的生化数据， 多态循环酶和生理和生物物理数据的 Na/K泵功能和糖苷敏感性的调节。 的 完成该项目的具体目标将促进我们的 了解Na/K泵的功能，并对其作用提供新的见解 在心脏生理学中。

The Na/K pump is an important membrane protein which has been extensively studied biochemically , physiologically, pharmacologically and biophysically. The Na/K pump is responsible for maintaining ion gradients across the cell membrane. In the heart, the Na/K pump is also important clinically for the inotropic and chronotropic actions produced by pharmacological or physiological alterations in Na/K pump activity. Despite this, the detailed mechanism of the Na/K pump is still elusive. The long range goal of this research is to understand how the Na/K pump: 1) is physiologically regulated in its activity, sensitivity to cardiac glycosides and site danger; 2) is regulate pathophysiologically (e.g. ischemia and congestive heart failure); and 3)is involved in the regulation of electrical and mechanical activity in the heart. This study will focus on the definition and utilization of a computer model to predict the behavior of the Na/K pump under a wide range of conditions, especially physiologically and clinically relevant conditions. A principle goal of this study will be to bring the biochemical information available on the Na/K pump to aid of physiological and biophysical experimentation. This work will provide a better understanding of Na/K pump function and should lead to new insights into the role of the Na/K pump in cardiac function. This proposal will complement ongoing research in this laboratory by incorporating into the model, data produced in experimental studies on the ionic and voltage dependence of Na/K pump activity as measured with the whole-cell patch-clamp technique in isolated myocytes. This study will utilize these experimental results, as well as published results from other laboratories, to construct a model of the Na/K pump. This model will incorporate the known biochemical data of a multistate cyclic enzyme and physiological and biophysical data on the regulation of Na/K pump function and glycoside sensitivity. The completion of the specific aims of this project will advance our understanding of Na/K pump function and provide new insight into its role in cardiac physiology.