METABOLISM AND ACTIVE ION TRANSPORT IN SKIN

这是一项支持研究离子传输特性的请求 穿过青蛙的皮膜。在过去的八年里，校长 调查人员将他的研究活动主要集中在模特上。 从这一理论工作中产生了一些定义明确和耐人寻味的 预测，如参与，不同，但合作 决定和调节全球环境的细胞内电解质域 多层上皮膜的转运特性。我们现在 要求适度增加支持，以评估这些模型及其 实验室里的预测。建议进行的研究将涉及 弗吉尼亚医学院的三名高级调查人员 首席研究员Donald Mikulecky博士，网络先驱 热力学模型和有经验的查尔斯·沃灵顿博士 青蛙皮肤运输研究的实验者。这件事的一个主要焦点 建议研究Na~+、K~+和C_1~-通量以及相关的 药物和药物非稳态(瞬变)期间的生物物理事件 荷尔蒙作用--从哇巴因的作用开始。这是在 与以往的大多数探讨“稳定”的通量研究形成鲜明对比 这一方法将使我们更深入地了解 参与上皮细胞对药物和药物反应的动力学 荷尔蒙。本研究提案将在以下背景下进行 非常活跃的博士后和博士后培训计划 弗吉尼亚医学院的生物学专业。博士后伙伴支持 因为这项工作将提高这个项目的生产率。作为回报， 该计划将继续成为这一领域的宝贵资产 生物医学教育，特别是应用的开拓性 网络热力学模型对生物系统的影响。这个项目 在以下学科中也有很强的健康相关影响 胃肠病学和肾脏医学，以及盐和水的代谢 它的荷尔蒙控制令人担忧。

This is a request for support of studies that characterize ion transport across frog skin membranes. Over the past eight years the principal investigator has focused his research activities largely on modelling. From this theoretical work have arisen some well defined and intriguing predictions such as the participation of distinct, but cooperative intracellular electrolyte domaines which determine and regulate global transport characteristics of multilayered epithelial membranes. We now request a modest increase in support to evaluate these models and their predictions in the laboratory. Studies are proposed that will involve three senior investigators at the Medical College of Virginia, the principal investigator, Dr. Donald Mikulecky, pioneer in network thermodynamic modelling and Dr. Charles Watlington, an experienced experimentalist in transport studies in frog skin. A major focus of this proposal is to study Na+, K+ and C1- fluxes, as well as related biophysical events in the nonsteady state (transient) period of drug and hormonal action - beginning with the action of ouabain. This is in contrast with most previous flux studies which have explored "steady state" conditions. This approach will give deeper insight into the dynamics involved in the responses of epithelial cells to drugs and hormones. This research proposal will be done within the context of a very active predoctoral and postdoctoral training program in membrane biology at the Medical College of Virginia. Postdoctoral fellow support for this work will enhance the productivity of this project. In return, this program will continue to be a valuable asset to this area of biomedical education and in particular, the pioneering of the application of network thermodynamic modelling to biological systems. This project also has strong health related implications in the disciplines of gastroenterology and renal medicine, inasmuch as salt and water metabolism and its hormonal control is concerned.