Osmoregulatory changes in Myo ‐inositol content and Na + / Myo ‐inositol contransport in rat cortical astrocytes

Exposure of cortical astrocytes to 325, 350, or 390 mosM culture media for 48 h caused a 1.4‐, 2.1‐, and 3.5‐fold increase, respectively, in cellular content of the compatible osmolyte myo ‐inositol. Elevated myo ‐inositol levels accounted for ∼56‐100% of the solute needed by the cells for complete volume regulation under hypertonic conditions. Myo ‐inositol accumulation was associated with 4‐5‐fold (peak rate) and 1.8‐2‐fold (steady‐state rate) increases in the rate of Na + ‐dependent myo ‐inositol uptake when cells were acclimated to 390 mosM culture medium for 12 h or 24‐96 h, respectively. When medium osmolality was elevated by 25 mosM, peak and steady‐state increases in myo ‐inositol uptake of 1.7‐fold and 1.3‐fold, respectively, were observed. Exposure to 390 mosM medium for 12‐48 h induced a 3‐8‐fold increase in cotransporter mRNA levels suggesting that the increase in myo ‐inositol uptake is brought about by increased cotransporter gene expression. Abrupt return of hypertonic cells to an isotonic medium induced a rapid increase in myo ‐inositol efflux and a return of cotransporter mRNA to control values in <2 h. In contrast, the cotransporter remained fully activated at hypertonic levels for 16 h. Between 16‐24 h after the transfer, the rate of myo ‐inositol uptake returned to control values. The remarkable sensitivity of the cotransporter to hypertonic stress indicates that upregulation of myo ‐inositol transport in glial cells is likely to occur in a variety of disease states that cause an elevation of plasma osmolality. Slow downregulation of the cotransporter may be responsible in part for the slow loss of myo ‐inositol and cerebral edema that occurs with too rapid correction of chronic plasma hypertonicity.