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.