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Biophys. J. BioFAST: First Published September 16, 2005. doi:10.1529/biophysj.105.065771
© 2005 by the Biophysical Society.


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BIOPHYSICAL THEORY AND MODELING

Modeling and Analysis of Calcium Signaling Events Leading to Long-Term Depression in Cerebellar Purkinje Cells

Nicholas Hernjak 1, Boris M. Slepchenko 1, Kathleen Fernald 2, Charles C. Fink 2, Dale Fortin 2, Ion I. Moraru 2, James Watras 2 and Leslie M. Loew 3*

1 University of Connecticut Health Center
2 Univeristy of Connecticut Health Center
3 Univ. of Connecticut Hlth. Ctr.

* To whom correspondence should be addressed. E-mail: les{at}volt.uchc.edu.

Submitted on May 4, 2005
Revised on June 23, 2005
Accepted on 26 August 2005


   Abstract
Modeling and simulation of the calcium signaling events that precede long-term depression of synaptic activity in cerebellar Purkinje cells are performed using the Virtual Cell biological modeling framework. It is found that the unusually high density and low sensitivity of inositol-1,4,5-trisphosphate receptors (IP3R) are critical to the ability of the cell to generate and localize a calcium spike in a single dendritic spine. The results also demonstrate the model's capability to simulate the supralinear calcium spike observed experimentally during coincident activation of the parallel and climbing fibers. The sensitivity of the calcium spikes to certain biological and geometrical effects is investigated as well as the mechanisms that underlie the cell's ability to generate the supralinear spike. The sensitivity of calcium release rates from the IP3R to calcium concentrations, as well as IP3 concentrations, allows for the calcium spike to form. The diffusion barrier caused by the small radius of the spine neck is shown to be important as a threshold radius is observed above which a spike cannot be formed. Additionally, the calcium buffer capacity and diffusion rates from the spine are found to be important parameters in shaping the calcium spike.

Key Words: Calcium buffers, Coincidence detection, Dendritic spines, IP3 receptors, Simulation




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Copyright © 2005 by the Biophysical Society.