METABOLISM AND ACTIVE ION TRANSPORT IN SKIN

这是一个支持描述离子传输特征的研究的请求 穿过青蛙的皮肤膜 在过去的八年里， 他的研究活动主要集中在建模上。 从这一理论工作中产生了一些明确的和耐人寻味的 预测，如参与不同的，但合作 细胞内电解质结构域，决定和调节全球 多层上皮细胞膜的运输特性。 我们现在 要求适度增加对评估这些模型及其 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研究人员， 首席研究员Donald Mikulecky博士，网络先驱 热力学模型和查尔斯·沃特灵顿博士，一位经验丰富的 青蛙皮肤运输研究的实验家。 其中一个主要焦点是 建议研究Na+，K+和C1-通量，以及相关的 药物非稳态（瞬态）期间的生物物理事件， 激素作用-从哇巴因开始。 这是 与大多数以前的通量研究相比， 状态”的条件。 这种方法将使人们更深入地了解 参与上皮细胞对药物反应的动力学， 荷尔蒙 这项研究计划将在一个 非常活跃的博士前和博士后培训计划在膜 在弗吉尼亚医学院学习生物学。 博士后支持 这项工作将提高该项目的生产力。 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，特别是应用的先驱 网络热力学模型的重要性。 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，因为作为盐和水的代谢 和它的荷尔蒙控制有关。

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.