Introduction to Computer Modeling in Physiology:
From Cell to Tissue
Joel Keizer and Leon Glass
Description
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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