Aluminium reduces glutamate-activated currents of rat hippocampal neurones.
The actions of aluminum on glutamate-activated currents of acutely isolated hippocampal neurones were investigated. N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and glutamate mediated currents were reduced by 50% in the presence of 1.4 micrograms ml-1 aluminium. Higher concentrations (> or = 2.7 micrograms ml-1) inhibited all currents completely and irreversibly. Additionally, successive application of agonists in the presence of 2.7 micrograms ml-1 aluminium resulted in non-specific membrane currents followed by the loss of the seal resistance. Application of aluminium per se had no influence on resting membrane current or voltage-activated sodium currents. The estimation of the concentration-response relationship of the action of aluminium on NMDA-activated currents revealed a threshold concentration < 0.27 micrograms ml-1. Our data indicate that glutamate receptors are putative sites of action in aluminium neurotoxicity.
Platt
B
B
Heinrich-Heine-Universität, Düsseldorf, Germany.
Haas
H
H
Büsselberg
D
D
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000535:Aluminum