MODELING OF NA/K PUMP ACTIVITY IN CARDIAC MYOCYTES

心肌细胞中 NA/K 泵活动的建模

• 批准号: 3421578
• 负责人: JOSEPH R STIMERS
• 金额: $ 8.09万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3421578
• 关键词: action potentials; computer simulation; enzyme mechanism; heart cell; heart function; mathematical model; micromanipulator; muscle cells; ouabain; sodium potassium exchanging ATPase; voltage /patch clamp

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.

Na/k泵是一种重要的膜蛋白，已广泛 从生化，生理，药理和 生物物理。 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 在临床上用于肌力和表年的作用 Na/K泵活性的药理或生理改变。 尽管如此，Na/K泵的详细机制仍然难以捉摸。 这项研究的远距离目标是了解Na/k泵： 1）在生理上受到其活性的调节，对心脏的敏感性 糖苷和现场危险； 2）在病理生理上受到调节（例如 缺血和充血性心力衰竭）； 3）参与了 调节心脏中的电和机械活性。 这项研究 将专注于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， 特别是生理和临床相关的条件。 一个 这项研究的主要目标是带来生化信息 可在Na/k泵上可用，以帮助生理和生物物理 实验。 这项工作将更好地了解NA/K 泵功能，应导致对Na/K的作用的新见解 泵中心脏功能。 该建议将补充正在进行的研究 在该实验室中，通过将其纳入模型，在 Na/k泵的离子和电压依赖性的实验研究 用孤立的全细胞斑块钳技术测量的活动 心肌细胞。 这项研究将利用这些实验结果以及 发表了其他实验室的结果，以构建 Na/k泵。 该模型将包含A的已知生化数据 多态环状酶以及生理和生物物理数据 调节Na/K泵功能和糖苷灵敏度。 这 该项目的具体目标的完成将推动我们的 了解Na/K泵功能，并提供有关其角色的新见解 在心脏生理学中。