Aluminium interferes with hippocampal calcium signaling in a species-specific manner.
Aluminium (Al) has been implicated in a number of neurodegenerative disorders and the disruption of calcium homeostasis has been proposed as a possible mechanism. To investigate ligand- and structure-specific effects of Al species, calcium imaging was used to probe the influence of five Al complexes - in comparison to inorganic Al (Al-S) - on N-methyl d-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) function in hippocampal neurontos. The Al complexes utilized comprised three Al-citrate species (AlCit1-3), Al-quinate (AlQ) and Al-N-phosphonomethyliminodiacetate (AlNTAP). Our results suggest variable toxicity among the Al compounds tested: Al-S most potently affected neurons, with a full and irreversible inhibition of NMDAR and VDCC signaling at 500 microM. At all concentrations tested (10, 100, and 500 microM), all Al compounds investigated inhibited NMDA responses, however, no dose-dependency was evident. Furthermore, striking differences were noted with respect to calcium responses via VDCC activation. AlCit2 reduced calcium responses at all concentrations tested, AlQ at 10 and 100 microM, and AlNTAP at 500 microM only. In contrast, AlCit1 and AlCit3 had no significant effect. Collectively, diversely structured Al-ligand species selectively affect neuronal membrane channel function. The distinct chemical reactivity of the various Al forms reflects their unique interactions with neuronal structures and is poised to explain the diverse facets of Al toxicity.
Nday
Christiane M
CM
Department of Chemical Engineering, Laboratory of Inorganic Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Drever
Benjamin D
BD
Salifoglou
Thanos
T
Platt
Bettina
B
D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D019343:Citric Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D017607:Aluminum Compounds; D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D019343:Citric Acid; C455846:aluminum citrate