Inward Operation of Sodium-Bicarbonate Cotransporter 1 Promotes Astrocytic Na Loading and Loss of ATP in Mouse Neocortex during Brief Chemical Ischemia.

Ischemic conditions cause an increase in the sodium concentration of astrocytes, driving the breakdown of ionic homeostasis and exacerbating cellular damage. Astrocytes express high levels of the electrogenic sodium-bicarbonate cotransporter1 (NBCe1), which couples intracellular Na homeostasis to regulation of pH and operates close to its reversal potential under physiological conditions. Here, we analyzed its mode of operation during transient energy deprivation via imaging astrocytic pH, Na, and ATP in organotypic slice cultures of the mouse neocortex, complemented with patch-clamp and ion-selective microelectrode recordings and computational modeling.

Modeling the heterogeneity of sodium and calcium homeostasis between cortical and hippocampal astrocytes and its impact on bioenergetics.

Emerging evidence indicates that neuronal activity-evoked changes in sodium concentration in astrocytes Na represent a special form of excitability, which is tightly linked to all other major ions in the astrocyte and extracellular space, as well as to bioenergetics, neurotransmitter uptake, and neurovascular coupling. Recently, one of us reported that Na transients in the neocortex have a significantly higher amplitude than those in the hippocampus. Based on the extensive data from that study, here we develop a detailed biophysical model to further understand the origin of this heterogeneity and how it affects bioenergetics in the astrocytes.