Influence of intracellular astrocyte acidification on the behavior of cell volume and intracellular sodium

Objective

In the time course of stroke or traumatic brain injury, astrocytes become acidotic and swollen. The question remains whether acidosis influences intracellular sodium concentrations and the astrocyte volume.

Methods

In cultured human astrocytoma cells, the effect of sodium propionate (NP) or ischemic medium (IM) on the cellular volume and intracellular hydrogen or sodium was documented by videomicroscopy and monitoring of the fluorescence of BCECF and SBFI, respectively. To quantify the participation of a Na⁺/H⁺ exchanger, a specific inhibitor (ethyl isopropyl amiloride [EIPA]) was added.

Results

Addition of NP resulted in an immediate intracellular acidosis, which only partially recovered after washout, and an immediate rise in intracellular sodium. NP introduced an increase of cell diameter to 120 ± 2%, followed by a reactive volume decrease within 15 min. EIPA was able to partially inhibit intracellular acidification (5 μM EIPA), and to abrogate cell swelling (10 μM EIPA). Comparable results were found with IM.

Conclusion

Intracellular astrocyte pH increase found during life-threatening brain conditions influence astrocyte swelling. Na⁺/H⁺ exchangers participate in these pathways.