Inhibition of AMPA Receptors by Zn2+

Fast excitatory synaptic transmission in the mammalian central nervous system is mediated by glutamate-activated α-amino-5-methyl-3-hydroxy-4-isoxazole propionate (AMPA) receptors. Glutamate binding to AMPA receptors leads rapid activation and desensitization. Synaptically released Zn2+ works as a neuromodulator many brain regions. Here, we show that inhibits GluA2(Q) homomeric an activity- voltage-dependent manner, showing pore block mechanism. At millimolar concentrations inhibition slow, residual non-desensitizing currents. However, GluA2 complex with auxiliary subunits γ2 γ8, promote larger activation. The extent of also dependent on charge at site 607, glutamine arginin editing, GluA2(R) has lower compared un-edited GluA2(Q). Although, GluA2(Q607E) mutation, observed patient exhibiting developmental delay, was higher inhibition. To mimic activity neurons, used repetitive pulses presence glutamate, significant both expressed HEK cells well native cortical neurons.