Title
Astrocytic Mechanisms Explaining Neural-Activity-Induced Shrinkage Of Extraneuronal Space
Abstract
Neuronal stimulation causes similar to 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+/HCO3- (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.
Year
DOI
Venue
2009
10.1371/journal.pcbi.1000272
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
potassium,systems biology,wild type,gene knockout,membrane potentials,na k atpase,extracellular space,osmosis,ion transport,sodium
Astrocyte,Membrane potential,Shrinkage,Biology,Biophysics,Biochemistry,Cotransporter,Sodium-Potassium-Exchanging ATPase,Bioinformatics,Potassium channel,Ion transporter,Stimulation
Journal
Volume
Issue
ISSN
5
1
1553-7358
Citations 
PageRank 
References 
13
2.02
0
Authors
9
Name
Order
Citations
PageRank
Ivar Østby1293.99
Leiv Oyehaug2254.05
Gaute T. Einevoll320926.15
Erlend A Nagelhus4132.35
Erik Plahte5475.37
Thomas Zeuthen6132.02
Catherine M. Lloyd719412.92
Ole P Ottersen8132.02
Stig W Omholt9799.24