Effect of external acidosis on basal and ATP-evoked calcium influx in cultured astrocytes.
The effect of lactic acidosis on calcium influx, accumulation and efflux was studied in primary cultures of neonatal cortical rat astrocytes. Treatment of cultures with 20 mM sodium lactate, pH 6.0, for 10-60 min resulted in a 35% reduction of 45Ca2+ influx. The decrease in calcium influx was pH dependent because a similar reduction was observed in cultures exposed to pH 6.0 without lactate, while no difference was observed in cultures treated with sodium lactate at pH 7.4. Calcium accumulation was also decreased by lactic acidosis (20% reduction), while calcium efflux was unaffected. Studies with lanthanum, an inhibitor of calcium transport, indicated that the effect of lactic acidosis was not due to non-specific leakage of calcium. The reduction in calcium influx was reversible, thereby indicating that the cells were not permanently damaged by lactic acidosis. In addition to basal calcium influx, stimulated influx (mediated by extracellular ATP, 100 microM) was also reduced by 20 mM sodium lactate, pH 6. These findings suggest that protonization of calcium channels or other calcium entry pathways leads to a reduction in calcium influx in astrocytes. This diminished calcium entry, by affecting calcium-dependent mechanisms necessary for such processes as volume regulation, glycogen metabolism, or regulation of ionic permeability, may alter the ability of astrocytes to elicit appropriate responses following CNS injury.
Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL 33125.
J T
JT
Neary
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Fu
A S
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Bender
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Norenberg
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D007773:Lactates; D003994:Bucladesine; D007811:Lanthanum; D000255:Adenosine Triphosphate; D002118:Calcium