Astrocytic Mechanisms Explaining Neural-Activity-Induced Shrinkage of Extraneuronal Space
Figure 4
Predicted dynamics of [TMA+]o and [K+]o in wild types and NKCC1 knockouts.
Predicted activity-dependent ECS volume dynamics in wild types (blue) and NKCC1 knockouts (or bumetanide-treated) (red) obtained by numerical solution of model equations (3) (see Methods) from t = 0 s to t = 100 s with enhanced neural activity for 10 s<t<30 s, using the parameter sets that satisfy all imposed constraints for (A) mc3, (B) mc4, (C) mc5. (D) Wild type and NKCC1 knockout of mc5 with active water transport through NKCC1 (in addition to AQP4-mediated passive water transport). In all plots, curves drawn with strong contrast are median values and the upper and lower curves drawn with weaker contrast define the boundaries between which 80% of all values in the used parameter sets fall. Lower insets show corresponding temporal evolution of the median ECS potassium level. (A) The upper inset displays the time-dependent potassium efflux (resp. sodium influx) rate profile (beta distribution with a = 2 and b = 16.0304) that is optimized for each model to yield potassium profiles in accordance with empirical observations (see Methods). The profiles corresponding to (B–D) resemble the one in (A) very closely (values for b are 15.18, 14.56 and 14.59, respectively). (D) The upper inset shows the AQP4-mediated water flux relative to zero. In mc3, NKCC1 is not included, hence NKCC1 knockout yields identical results as the wild type (A).