SWELLING AND DAMAGE OF GLIAL-CELLS BY LACTACIDOSIS AND GLUTAMATE - EFFECT OF ALPHA-TRINOSITOL

The therapeutical efficacy of alpha-trinositol (D-myo-inositol-1,2,6-t risphosphate), an isomer of the intracellular messenger IP3, was analy zed on cytotoxic swelling and damage of glial cells in vitro from lact acidosis or glutamate. C6 glioma cells suspended in a physiological me dium were either exposed to pH 5.0 by administration of lactic acid, o r to 1 mM glutamate. Cell swelling and viability were quantified by fl ow cytometry. Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min whereas alpha-trinositol was reducing the swelling response by approximately 25% (P < 0.01). In addition, a t pH 5.0 the fraction of viable cells was lowered from 94.3 +/- 0.2% ( control) to only 53.8 +/- 3.1% after 60 min. alpha-Trinositol was foun d to protect also cell viability; at 60 min of lactacidosis 70.2 +/- 1 .6% of the cells still were viable (P < 0.01). The addition of glutama te (1 mM) to the cell suspension led to a steady increase in cell size , reaching 110% of control at 120 min, irrespectively of whether alpha -trinositol was added or not. (C) 1997 Elsevier Science B.V.