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                                           BIOINFORMATICS COLLOQUIUM
					       College of Science
                                            George Mason University
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                       Stochastic Modeling of Local and Global Intracellular Calcium Dynamics

 
                                               Gregory Smith, Ph.D.

                                              Associate Professor 
                                Department of Applied Science, William & Mary

Abstract:
Although there is consensus that calcium (Ca) puffs and sparks 
arise from the cooperative action of multiple intracellular Ca channels,  
the precise relationship between single-channel kinetics and the  
collective phenomena of stochastic Ca excitability and oscillations  
is not well understood. Here we present and analyze a stochastic  
automata network model of instantaneously coupled Ca-regulated 
Ca channels that gives insight into how the stochastic dynamics of an  
individual Ca release site depends on channel density and the  
presence or absence of Ca inactivation. The relationship between  
such stochastic Ca release site dynamics and global Ca responses 
will then be discussed in the context of a novel probability density  
approach to modeling whole cell Ca dynamics. The method involves 
coupling ODEs for the bulk cytosolic and ER [Ca] to advection- 
reaction equations for the probability density of the [Ca] in  
cytosolic and lumenal domains associated with each channel and  
conditioned on channel state. The probability density approach is  
computationally more efficient than explicitly spatial Monte Carlo  
simulations and the representation of local Ca signals inherent in  
the probability density approach is more realistic than conventional  
stochastic compartmental models.