The mechanism of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor desensitization after removal of glutamate.

We have examined responses of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors in the chick nucleus magnocellularis to pairs of pulses of glutamate and determined the extent of desensitization and the rate of recovery. Receptors recovered from desensitization with a time constant of 16 ms, regardless of the concentration or duration of the conditioning pulse. Even with very brief conditioning pulses, evoking submaximal currents, desensitization occurred at a consistent rate after the removal of free ligand. A quantitative kinetic model based on these data shows that receptors must desensitize from a closed state. The results provide evidence that very brief exposure to glutamate, on the time scale of uniquantal synaptic transmission, will result in a significant reduction in sensitivity of postsynaptic receptors.