Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission

Na+-activated K+ (K-Na) channels are expressed in neurons and are activated by Na+ influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that KNa channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of KNa channels by Na+ transients via AMPA receptors shapes the decay of AMPA-mediated current as well as the amplitude of the synaptic potential. Thus, the coupling between KNa channels and AMPA receptors by synaptically induced Na+ transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.