Electrodiffusive Model for Astrocytic and Neuronal Ion Concentration Dynamics

44Citations
Citations of this article
93Readers
Mendeley users who have this article in their library.

Abstract

The cable equation is a proper framework for modeling electrical neural signalling that takes place at a timescale at which the ionic concentrations vary little. However, in neural tissue there are also key dynamic processes that occur at longer timescales. For example, endured periods of intense neural signaling may cause the local extracellular K+-concentration to increase by several millimolars. The clearance of this excess K+ depends partly on diffusion in the extracellular space, partly on local uptake by astrocytes, and partly on intracellular transport (spatial buffering) within astrocytes. These processes, that take place at the time scale of seconds, demand a mathematical description able to account for the spatiotemporal variations in ion concentrations as well as the subsequent effects of these variations on the membrane potential. Here, we present a general electrodiffusive formalism for modeling of ion concentration dynamics in a one-dimensional geometry, including both the intra- and extracellular domains. Based on the Nernst-Planck equations, this formalism ensures that the membrane potential and ion concentrations are in consistency, it ensures global particle/charge conservation and it accounts for diffusion and concentration dependent variations in resistivity. We apply the formalism to a model of astrocytes exchanging ions with the extracellular space. The simulations show that K+-removal from high-concentration regions is driven by a local depolarization of the astrocyte membrane, which concertedly (i) increases the local astrocytic uptake of K+, (ii) suppresses extracellular transport of K+, (iii) increases axial transport of K+ within astrocytes, and (iv) facilitates astrocytic relase of K+ in regions where the extracellular concentration is low. Together, these mechanisms seem to provide a robust regulatory scheme for shielding the extracellular space from excess K+. © 2013 Halnes et al.

Figures

  • Figure 1. A two domain-model for ion concentration dynamics in the intra- and extracellular space, when macroscopic transport is essentially one-dimensional. (A) A piece of neural tissue with cross section area Aref and an arbitrary extension l in the xdirection. The tissue contains cells (dark grey) that participate in the transport process, and cells that do not (light grey). (B) The interior of all participatory cells represented as a single, equivalent cylindrical cable (I ), coated by ECS (E). The geometry is specified by three parameters, where aI and aE are, respectively, the fractions of Aref occupied by the ICS of participatory cells and the ECS, and OM (m {1) is the amount of membrane area per tissue volume (or, equivalently, the circumference of the equivalent cable divided by Aref ). Due to the presence of other cells (non-participatory), we generally have that aIzaEv1. The concentration of ion species k is denoted ½k n where n represents domain I or E. Ionic movement is described by the transmembrane flux density (jkM ) and the longitudinal flux densities due to electrical migration (jfkn) and diffusion (j d kn). doi:10.1371/journal.pcbi.1003386.g001
  • Table 1. List of symbols and definitions.
  • Table 2. Model parameters.
  • Figure 3. Astrocyte model. A representative astrocyte (I) exchanging ions with the ECS (E). As indicated, ions could cross the astrocytic membrane via passive Na+ or Cl2 channels, via the K+ Kir channel or the Na+/K+-pump. Ions could also be transported longitudinally by electrical migration jfkn or diffusion j d kn through the ICS (n~I ) or ECS (n~E). The cation-exchange input was a constant influx of K+ and efflux of Na+ to/ from the ECS of the input zone (defined as the region 0vxvl=10). The cation-exchange output was an efflux of K+ and influx Na+ from/to the ECS. The output was proportional to the local K+-concentration, and occurred over the whole axis. The decay zone was defined as the part of the axis where no input was applied (xwl=10), i.e., the region where there was a net efflux of K+ from the system. doi:10.1371/journal.pcbi.1003386.g003
  • Figure 4. Dynamics and steady state profiles for the astrocyte/ ECS-system. (A–D) Dynamics of selected variables in a point (x~0) in the input zone. (E–H) Spatial profiles of selected variables at a time t~400s, when the system was in steady state. The constant cationexchange input was applied to the ECS of the input (0vxv0:03mm) zone from t~100s to t~400s. (A) The input and output flux densities of K+ to the point x~0. We recall that the Na+ input/output (not shown) was the opposite of that of K+: jinNa~{j in K and j out Na~{j out K . (B,D) During the input, ion concentrations in the ECS and ICS changed, but reached steady state after about 10–50 s after stimulus onset. (B) ½Kz E (at x~0) had then increased by about 7.7 mM with respect to the baseline value. (C) ½Kz I had increased by about 12.5 mM due to uptake by the astrocyte. (D) The astrocytic membrane potential had been depolarized to about 259 mV at x~0. The impact of the input was smaller outside the input zone. (F–H) Deviations from the baseline ionic concentrations and vM typically decreased with x. Far away from the input zone (x~0:3mm), the conditions were close to the baseline conditions. (B–C, F–G) Ionic concentrations were represented in terms of deviations from resting concentrations: D½k n~½k n{½k 0 n for n~I ,E. For direct comparison with ion concentrations, the charge density was represented as an equivalent concentration of unit charges ½ez n . doi:10.1371/journal.pcbi.1003386.g004
  • Figure 5. Transports in the astrocyte/ECS system during steady state. (A) Total flux densities into system (input{output). (B) Transmembrane flux densities. (C–F) Longitudinal flux densities due to (C) electrical migration in the ECS, (D) electrical migration in the ICS, (E) diffusion in the ECS and (F) diffusion in the ICS. (A–D) To aid comparison, flux densities jkn were scaled by the relative area fraction an (e.g., if aEjkE~aI jkI , I and E carry the same the net flux of ion species k). (G) A flow chart that qualitatively summarizes the essential information in (A–F), showing the main transport routes of K+ and Na+ during SS (Cl2 excluded from the overview). K+ generally entered the system in the input zone and left the system from some point along the astrocyte axis. The transport route of K+ (from entering to leaving the system) was predominantly intracellular, demonstrating the astrocyte’s efficiency as a spatial buffer. Na+ entered in the decay zone and left from the input zone. Na+ transport predominantly took place in the ECS. The illustration (G) is qualitative - longer arrows mean higher flux densities, but the mapping from (A–F) to (G) is not quantitatively exact. The input zone was in the region 0vxv0:03mm. Units on the yaxis are mmol=(m2s) in all panels. doi:10.1371/journal.pcbi.1003386.g005
  • Figure 6. Membrane mechanisms involved in spatial K+buffering. (A) The K+ reversal potential (eK ) was more negative than vM at all points along the x-axis. The Kir-channel thus exclusively mediated an outward K+-current. (B) In the input zone eK was close to vM , and the outward Kir-current was small compared to the inward current through the Na+/K+-pump. In the decay zone, the outward Kircurrent was bigger, and dominated over the inward current through the Na+/K+-pump. Therefore, the astrocyte took up up K+ in the input zone, and released K+ in the decay zone (as indicated by arrows in (B)). doi:10.1371/journal.pcbi.1003386.g006
  • Figure 7. Sensitivity analysis. Sensitivity of ½Kz maxE (maximal extracellular ½Kz in the input zone) to variation in selected model parameters. (A) Sensitivity to input flux density (jin) and the output rate constant (kdec). Similar values of ½Kz maxE &11mM were obtained for the three marked data points: (i) black: kdec~2:9|10 {8 m=s, jin~5:5|10 {8 mol=(m2s) (default conditions), (ii) green: kdec~1|10 {8 m=s, jin~3|10 {8 mol=(m2s), and (iii) red: kdec~5|10 {8 m=s, jin~8|10 {8 mol=(m2s). B–D) Sensitivity to the length of the input zone (liz), and tortuosities in the ECS (lE ) and ICS (lI ). (E– H) Sensitivity of ½Kz maxE and ½Kz 0 E (baseline extracellular ½Kz ) to membrane conductances (gK , gNa and gCl ), and the maximal Na +/K+-pump rate (Pmax). D½Kz E~½Kz max E (i){½Kz 0 E . (B–H) The legend applies to all panels. Black (i), red (ii) and green (iii) lines correspond to the input-parameter combinations marked in (A). doi:10.1371/journal.pcbi.1003386.g007

References Powered by Scopus

Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization

2344Citations
N/AReaders
Get full text

Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia.

910Citations
N/AReaders
Get full text

Extracellular space structure revealed by diffusion analysis

803Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow

195Citations
N/AReaders
Get full text

Astrocytic modulation of neuronal excitability through K<sup>+</sup> spatial buffering

168Citations
N/AReaders
Get full text

The glymphatic system: Current understanding and modeling

131Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Halnes, G., Østby, I., Pettersen, K. H., Omholt, S. W., & Einevoll, G. T. (2013). Electrodiffusive Model for Astrocytic and Neuronal Ion Concentration Dynamics. PLoS Computational Biology, 9(12). https://doi.org/10.1371/journal.pcbi.1003386

Readers over time

‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24‘250481216

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 38

57%

Researcher 14

21%

Professor / Associate Prof. 13

19%

Lecturer / Post doc 2

3%

Readers' Discipline

Tooltip

Neuroscience 24

48%

Agricultural and Biological Sciences 10

20%

Engineering 9

18%

Computer Science 7

14%

Article Metrics

Tooltip
Mentions
Blog Mentions: 1
Social Media
Shares, Likes & Comments: 21

Save time finding and organizing research with Mendeley

Sign up for free
0