Na⁺-mediated coupling between AMPA receptors and K_Na 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 K_Na channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of K_Na 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 K_Na channels and AMPA receptors by synaptically induced Na⁺ transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.