PRESS - AMPAR

Although it is well known that the glutamate affinity for AMPA receptors is submicromolar, ligand-dependent currents are observed only at submillimolar glutamate concentrations, suggesting a non-equilibrium mechanism of dose-dependent signaling.

Here, we developed a mathematical model that leverages published reaction rates to demonstrate that AMPA receptors operate within a pre-equilibrium sensing and signaling (PRESS) regime. By functioning before equilibrium binding, AMPARs exploit a transient dynamic range at high ligand concentrations. Our model reveals that fast desensitization is a key transition enabling this PRESS mechanism.