Aluminum neurotoxicity effects on intracellular Ca2+ homeostasis in the rat cerebral cortex

Studies have suggested that aluminum,a neurotoxic metal,is involved in the progression of neurodegenerative diseases.Previous studies have confirmed that aluminum influences intracellular Ca2+ homeostasis.However,it remains unclear whether aluminum increases or decreases intracellular Ca2+ concentrations.The present study demonstrated that Al3+ competitively binds to calmodulin(CaM),together with Ca2+,which resulted in loss of capacity of CaM to bind to Ca2+,leading to increased [Ca2+]i.Al3+ stimulated voltage-gated calcium channels on cell membranes,which allowed a small quantity of Ca2+ into the cells.Al3+ also promoted calcium release from organelles by stimulating L-Ca2+ α1c to trigger calcium-induced calcium release.Although Al3+ upregulated expression of Na+/Ca2+ exchanger mRNA,increased levels of Ca2+ and Na+/Ca2+ exchanger did not maintain a normal Ca2+ balance.Al3+ resulted in disordered intracellular calcium homeostasis by affecting calcium channels,calcium buffering,and calcium expulsion.