Models of Biological Transport in Ionic Channels

研究者开发，分析和计算离子通道的生物运输模型。现在已知离子通道通过细胞膜介导重要的电活动。膜片钳的发现使这种电流的实验验证成为可能。理论预测是通过一系列模型进行的。对于较简单的模型，寻求可能行为的分类，并仔细研究动力学。特别是对门控进行了详细的分析；这包括正常和异常行为。通过计算蛋白质的热交换，可以了解通道与其周围环境的关系。此外，一个复杂的渐近过程产生了一个高场模型，特别适合于通道，但最初是为半导体开发的。这一建议得益于研究人员以前在半导体建模方面的经验。电扩散的共同线索导致了惊人相似的数学模型。这种类比促进了一些有趣的研究，以及一些挑衅性的猜测。其中之一是研究温度在通道中的作用。另一种是所谓的主动运输，以及与ATP分子的联系。离子通道是细胞膜上的蛋白质分子，与多种应用有关，一方面是药物受体，另一方面是大脑中的不规则门控和精神疾病。研究者和他在数学和生物学领域的同事们建立了通道电和能量活动的模型。该项目极大地受益于为离子通道和半导体器件开发的数学模型的相似性。电流是由通道中的离子产生的，而半导体中的电子和空穴也起着类似的作用。在通道孔中，强大的电场与强烈的生物活性共存。首席研究员和他的同事们研究了这些类比，以及生物重要性的单独问题，包括用数学术语解释与通道打开和关闭相关的脉冲和与主动运输相关的能量学的可能性，包括各种离子“泵”的作用。这项工作旨在阐明围绕能量交换、加热和温度变化的细节。该项目使用数学分析和广泛的计算机模拟。

Jerome 9704458 The investigator develops, analyzes, and computes with models of biological transport for ionic channels. Ionic channels are now known to mediate significant electrical activity through cellular membranes. The discovery of the patch clamp has made experimental verification of such electrical currents possible. Theoretical predictions proceed through a hierarchy of models. For the simpler models, categorization of possible behavior is sought, and the dynamics carefully studied. In particular, gating is analyzed in great detail; this includes both regular and anomalous behavior. An understanding of the relation of the channel to its ambient environment is achieved through the calculation of the heat exchange of the protein. In addition, a complex asymptotic procedure yields a high field model, particularly appropriate for channels, yet originally developed for semiconductors. This proposal benefits from the investigators' previous experience in semiconductor modeling. The common thread of electro-diffusion leads to mathematical models of surprising similarity. This analogy has facilitated some interesting studies, as well as some provocative conjectures. One of these deals with the role of temperature in channels. Another deals with so-called active transport, and the association with the molecule ATP. Ionic channels are protein molecules in cell membranes, and have been linked to such diverse applications as drug receptors on the one hand, and irregular gating in the brain and mental illness on the other hand. The investigator and colleagues in mathematics and biology model the electrical and energetic activity of channels. The project greatly benefits from the similarity in the mathematical models developed for both ionic channels and semiconductor devices. Whereas electrical currents are induced by ions in channels, a similar role is played by electrons and holes in semiconductors. Powerful electric fields coexist with int ense biological activity in the channel pore. The principal investigator and his colleagues study these analogies, as well as separate issues of biological import, including the possibility of explaining, in mathematical terms, the pulses associated with the opening and closing of channels and the energetics associated with active transport, including the action of various ion "pumps." The work aims to clarify details surrounding energy exchange, heating, and temperature variation. The project uses both mathematical analysis and extensive computer simulations.