Cooling2007_IP3transients_CardiacMyocyte

This a model from the article:

Modeling hypertrophic IP3 transients in the cardiac myocyte.

Cooling M, Hunter P, Crampin EJ.
Biophys J2007 Nov 15;93(10):3421-33
17693463,

Abstract:

Cardiac hypertrophy is a known risk factor for heart disease, and at the
cellular level is caused by a complex interaction of signal transduction
pathways. The IP3-calcineurin pathway plays an important role in stimulating the
transcription factor NFAT which binds to DNA cooperatively with other
hypertrophic transcription factors. Using available kinetic data, we construct a
mathematical model of the IP3 signal production system after stimulation by a
hypertrophic alpha-adrenergic agonist (endothelin-1) in the mouse atrial cardiac
myocyte. We use a global sensitivity analysis to identify key controlling
parameters with respect to the resultant IP3 transient, including the
phosphorylation of cell-membrane receptors, the ligand strength and binding
kinetics to precoupled (with G(alpha)GDP) receptor, and the kinetics associated
with precoupling the receptors. We show that the kinetics associated with the
receptor system contribute to the behavior of the system to a great extent, with
precoupled receptors driving the response to extracellular ligand. Finally, by
reparameterizing for a second hypertrophic alpha-adrenergic agonist,
angiotensin-II, we show that differences in key receptor kinetic and membrane
density parameters are sufficient to explain different observed IP3 transients
in essentially the same pathway.

This model was taken from the
CellML repository and automatically converted to SBML.

The original model was:

Cooling M, Hunter P, Crampin EJ. (2007) - version02

The original CellML model was created by:

Cooling, Mike,

[e-mail]

The University of Auckland

The Bioengineering Institute

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