Ostby, Omholt, Oyehaug, Einevoll, Nagelhus, Plahte, Zeuthen, Voipio, Lloyd, Ottersen, 2008

Model Status

This cellML model is known to run in OpenCell and COR to recreate the published results. The units have been checked and they are consistent.

Model Structure

ABSTRACT: Neuronal stimulation causes approximately 30% shrinkage of the extracellular space (ECS) between neurons and surrounding astrocytes in grey and white matter under experimental conditions. Despite its possible implications for a proper understanding of basic aspects of potassium clearance and astrocyte function, the phenomenon remains unexplained. Here we present a dynamic model that accounts for current experimental data related to the shrinkage phenomenon in wild-type as well as in gene knockout individuals. We find that neuronal release of potassium and uptake of sodium during stimulation, astrocyte uptake of potassium, sodium, and chloride in passive channels, action of the Na/K/ATPase pump, and osmotically driven transport of water through the astrocyte membrane together seem sufficient for generating ECS shrinkage as such. However, when taking into account ECS and astrocyte ion concentrations observed in connection with neuronal stimulation, the actions of the Na(+)/K(+)/Cl(-) (NKCC1) and the Na(+)/HCO(3) (-) (NBC) cotransporters appear to be critical determinants for achieving observed quantitative levels of ECS shrinkage. Considering the current state of knowledge, the model framework appears sufficiently detailed and constrained to guide future key experiments and pave the way for more comprehensive astroglia-neuron interaction models for normal as well as pathophysiological situations.

Schematic diagram of the model. In the excited state there is an exchange of sodium and potassium ions across the neuron membrane and the cotransporters in the astrocyte are active.

The original paper reference is cited below:

Astrocytic mechanisms explaining neural-activity-induced shrinkage of extraneuronal space, Ostby I, Oyehaug L, Einevoll GT, Nagelhus EA, Plahte E, Zeuthen T, Lloyd CM, Ottersen OP, and Omholt SW, 2009, PLoS Computational Biology, 5, 1, e1000272. PubMed ID: 19165313

To begin collaborating on this work, please use your git client and issue this command: