Astrocytic processes explaining neural activity-induced shrinkage of extraneuronal space
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
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.
model diagram
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
wi
ratio of astrocyte volume to astrocyte area
w_tot
ECS volume to area ratio
N_Nai
number of sodium ions in the astrocyte
N_Ki
number of potassium ions in the astrocyte
N_HCO3i
number of bicarbonate ions in the astrocyte
N_Cli
number of chloride ions in the astrocyte
N_Nao
number of sodium ions in the extracellular space
N_Ko
number of potassium ions in the extracellular space
N_HCO3o
number of bicarbonate ions in the extracellular space
N_Clo
number of chloride ions in the extracellular space
J_NaKATPase
sodium-potassium ATPase pump
I_K
voltage-dependent potassium current
I_Cl
voltage-dependent chloride current
I_Na
voltage-dependent sodium current
neuron
neurobiology
electrophysiological
astrocyte
extracellular space
aquaporin
In collaboration with the original model author I added a piecewise equation to define a time-dependent parameter called "y". This was added in order to get the CellML model to be able to reproduce a stimulated state.
I
Ostby
Catherine
Lloyd
May
E
Nagelhus
keyword
2008-06-00 00:00
Simulation metadata has been added.
cmeta:id added to variable N_Ko
Catherine
Lloyd
May
60
10000
0.01
T
Zeuthen
Catherine Lloyd
Auckland Bioengineering Institute
2008-05-22T00:00:00+00:00
L
Oyehaug
G
Einevoll
T
S
Omholt
W
The University of Auckland, Auckland Bioengineering Institute
Astrocytic processes explaining neural-activity-induced shrinkage of extraneuronal space
5
e1000272
O
Ottersen
P
C
Lloyd
M
This is a CellML description of Ostby et al.'s 2008 mathematical model of neuronal activity and shrinkage of the extraneuronal space.
E
Plahte
19165313
PLoS Computational Biology
c.lloyd@auckland.ac.nz
Catherine
Lloyd
May
2008-09-29T10:33:25+13:00
2008-05-26T08:41:32+12:00
2008-06-19T10:45:41+12:00
Ostby et al.'s 2008 mathematical model of neuronal activity and shrinkage of the extraneuronal space.
James
Lawson
Richard
Used COR to correct the units such that there are now no error messages at all.
J
Voipio