Introduction to Computer Modeling in Physiology:
From Cell to Tissue

Joel Keizer and Leon Glass


Over the past several decades progress in the measurement of rates of molecular and cellular processes combined with a rapid advance in computer technology has initiated a revolution in our understanding of dynamic phenomenon in cells and tissues. Generally speaking, the phrase ``dynamic phenomenon'' refers to any process or observable that changes over time. These include changes that occur in single cells, such as spikes or bursts of electrical activity in the plasma membrane, intracellular signaling via receptors and second messengers, or more complex processes that involve spreading or coordination of activity over tissues or between various organs in the body. Clusters of cells may act like transducers. For example, pancreatic islets respond to an elevation of blood glucose levels by secreting insulin, and the sinus node of the heart changes its rate as a function of circulating levels of hormones. In this tutorial we describe some of the diverse dynamic phenomena that can be treated by current computational and analytical methods. We present simplified models, such as the Poincare oscillator for limit cycle oscillation and the ``fire-diffuse-fire'' model that describes intracellular calcium waves in muscle cells. We also describe a variety of complex models such as the ionic models developed for cardiac cells and tissues and glucose-stimulated electrical activity in insulin secreting pancreatic beta cells. In our presentation we stress that models should do more than simply reproduce observed phenomena. By providing insight into mechanisms they should make it possible to predict the results of new experiments. Moreover, the theoretical advances should provide novel strategies for drug development and medical devices.

Biographical Sketches

Joel Keizer is Professor of Biological Science, Chemistry, and Director, Institute of Theoretical Dynamics at the University of California, Davis. After working for two decades on foundational questions dealing with the statistical thermodynamics of far-from-equilibrium processes, he has spent the past 10 years working in cell biophysics.

Leon Glass is Professor of Physiology, McGill University, Montreal, Quebec, Canada. Since receiving a PhD in Chemical Physics from the University of Chicago in 1968, he has been working on problems involving applications of mathematical methods from nonlinear dynamics to study dynamics in physiological systems with special emphasis on the analysis of normal and abnormal cardiac rhythms. He is the coauthor (with Michael Mackey) of "From Clocks to Chaos: The Rhythms of Life" (Princeton, 1988) which forms a good background for this tutorial.

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