Zinc changes AMPA receptor properties: results of binding studies and patch clamp recordings.
The influence of zinc ions on alpha-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 CaCl2 (2.5 mM) and KSCN (100 mM). This effect was associated with a dramatic increase in Bmax 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 microM). 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.
Bresink
I
I
Department of Pharmacology, Merz+Co., Frankfurt, Germany.
Ebert
B
B
Parsons
C G
CG
Mutschler
E
E
D000818:Animals; D002478:Cells, Cultured; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D018091:Receptors, AMPA; D015032:Zinc