Correlations between energy metabolism, ion transport, and water content in astrocytes

Abstract

Energy metabolism, ion transport, and water content are interrelated in mechanisms of homeostasis of the brain intracellular and extracellular environment. The simplest model of cell homeostasis, the pump–leak hypothesis, incorporates basic relationships between these variables. Although this model accurately calculates steady-state cell volumes, ion concentrations, and metabolic rates, it fails to predict dynamic changes in these properties during elevated extracellular potassium, metabolic inhibition, and osmotic swelling. We have investigated relationships between ions, energy metabolism, and water content in cerebral astrocytes cultured from the neonatal rat. These cells swell more in hypoosmotic phosphate-buffered saline (PBS) containing NaCl than in hypoosmotic PBS with all NaCl replaced equiosmotically by sucrose. Unidirectional Na+ influx also is greater in cells suspended in hypoosmotic, compared with isoosmotic PBS. These data suggest that astrocytes possess a cell volume dependent mechanism of Na+ accumulation. The influx of Na+ during swelling may be coupled to metabolism via Na–K ATPase and may contribute to the sustained swelling of astrocytes observed in hypoosmotic swelling of the brain in situ.Key words: sodium, hypoosmolality, sodium–potassium adenosine triphosphatase, mathematical modeling.