Zinc changes AMPA receptor properties: Results of binding studies and patch clamp recordings

Abstract

The influence of zinc ions on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors was investigated using binding studies with [ 3H]AMPA to rat cortical membranes and patch clamp recordings from cultured superior colliculus neurones. In Tris-HCl buffer, zinc (1–10 mM) significantly increased the specific binding of [ 3H]AMPA whereas this increase was negligible in the presence of CaCl 2 (2.5 mM) and KSCN (100 mM). This effect was associated with a dramatic increase in B max but a decrease in both agonist and antagonist affinity. Association and dissociation experiments showed that equilibrium [ 3H]AMPA binding is reached with faster kinetics in the presence of zinc. At low concentrations (0.3 mM) zinc also concentration-dependently potentiated both peak and plateau components of whole cell current responses to AMPA (100 μM). This effect was accompanied by a reduction of the degree, and slowing of the rate, of AMPA receptor desensitisation. In contrast, higher concentrations of zinc (1–3.0 mM) inhibited AMPA responses to some degree, but slowed desensitisation further. This ability of zinc to change AMPA receptor properties may be relevant to neurotoxicity associated with AMPA receptor activation.