Calcium modulates aluminum neurotoxicity and interaction with neurofilaments

We examined the influence of calcium on neurotoxicity of AlCl3 and Al-lactate toward differentiated NB2a/d1 cells. Apart from induction of perikaryal neurofibrillary inclusions, AlCl3 at 1 mM induced no obvious additional signs of toxicity when added to culture medium in the presence of the normal medium CaCl2 content of 1.8 mM, nor when extracellular calcium was decreased by the addition to the medium of 0.9 mM EDTA. Increasing the extracellular CaCl2 concentration by fivefold was only marginally toxic, but in the presence of AlCl3, reduced viable cell numbers by well over 50% as compared to control cultures, and by approximately 50% vs fivefold CaCl2 alone. A twofold increase in extracellular CaCl2 did not increase the percentage of cells exhibiting Bielschowsky-positive perikarya, but induced a near doubling in the percentage of cells exhibiting accumulations in the presence of 1 mM Al-lactate. AlCl3 (1 mM) retards the electrophoretic migration of NF subunits on SDS-gels. This effect was eliminated by withholding CaCl2 from the incubation mixture and including 5 mM EDTA during incubation of cytoskeletons with AlCl3. The presence of CaCl2 alone did not alter NF migration. These findings underscore the possibility that multiple factors, including those that compromise general neuronal homeostasis, may contribute to neurofibrillary pathology.