Stochastic Modeling of Ion Channels

9625384赖斯和弗雷德金摘要 研究人员对离子通道的随机行为建模和膜片钳记录的统计分析中出现的一些问题进行了研究：（1） 研究动力学参数的最大似然估计，特别注意计算方面以及动力学模型的解释和评估;（2）研究在分析多通道记录时出现的问题;（3）研究 基于随机微分方程的模型的实用性，与通常在该领域中使用的具有离散状态空间的马尔可夫模型相反。 离子通道是允许电流以离子形式穿过细胞膜的大蛋白质。 这些通道是神经肌肉系统中电流传导的基本单位，并且各种离子通道的相互关系塑造了系统的电信号。 离子通道的研究不仅有助于对神经肌肉系统进行更深入的基础了解，而且还因为离子通道功能与各种神经肌肉疾病有关，并且因为药物产品（如麻醉剂）以离子通道为目标。 一种被称为“单通道膜片钳”的实验技术允许进行记录，这提供了关于这些通道的重要信息。 所记录的海流的明显的随机特性导致了对渠道动态的统计模型的广泛使用以及数据处理的统计技术的使用。 由这种记录产生的非常大量的数据造成了大量的计算问题，必须解决这些问题，以便可以有效地提取关于信道的重要信息。 这个跨学科的建议主要涉及有效的统计和计算方法的发展。

9625384 Rice and Fredkin ABSTRACT The investigators do research on a number of problems that arise in modeling the stochastic behavior of ion channels and in the statistical analysis of patch clamp recordings: (1) investigations of maximum likelihood estimation of kinetic parameters with particular attention to computational aspects and the interpretation and assessment of the kinetic models; (2) investigation of problems which arise in the analysis of records in which multiple channels are present; (3) investigation of the utility of models which are based on stochastic differential equations in contrast to Markov models with a discrete state space, which have typically been used in the field. Ion channels are large proteins that allow current in the form of ions to pass across cell membranes. These channels are the fundamental units of current conduction in the neuromuscular system and the interrelationships of a large variety of ion channels shape the electrical signals of the system. The study of ion channels is useful not only for the purpose of deeper basic understanding of the neuromuscular system, but also because ion channel function is implicated in various neuromuscular diseases and because pharmaceutical products, such as anesthetics, are targeted at ion channels. An experimental technique known as the "single channel patch clamp" allows recordings to be made which provide important information about these channels. The apparently random character of the recorded currents has led to the widespread use of statistical models for the dynamics of the channels and to the use of statistical techniques of data processing. The very large quantity of data produced by such recordings poses substantial computational problems which must be resolved in order that important information about the channels can be extracted efficiently. This interdisciplinary proposal is primarily concerned with the development of effective statistical and computational methodology.