Abstract
Astrocytes are vital for the maintenance of ion and transmitter homeostasis in the extracellular space, with the inward Na⁺ gradient playing a pivotal role in these processes. Earlier studies not only reported a low baseline Na (+) concentration ([Na (+) ]) in astrocytes, but also suggested an equilibration of [Na (+) ] within the gap-junction-coupled syncytium. This is consistent with the view that the basic homeostatic properties of astrocytes are largely identical due to their critical role in brain function. Here, we used multi-photon fluorescence lifetime imaging for a quantitative determination of astrocytic [Na (+) ] in mouse forebrain tissue slices and in vivo . Contrary to the prevailing notion of a rather uniform Na⁺ distribution, we detected a previously unobserved subcellular and cellular heterogeneity in astrocytic [Na (+) ], accompanied by differences in the capacity for Na (+) /K (+) -ATPase (NKA)-mediated uptake of extracellular K (+) . Biophysical modelling showed that this heterogeneity can be replicated by the reported differential expression of NKA isoforms in astrocytes together with a different strength of Na (+) influx over the plasma membranes. Altogether, our results thus suggest the existence of functionally distinct astrocytes and astrocyte subdomains in which Na (+) homeostasis is locally adapted to the specific requirements of surrounding neural networks.