Stochastic Modeling of Ion Channels

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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.