  Modulation of the properties of AMPA receptors at the post-synaptic membrane
is one of the main suggested mechanisms behind synaptic plasticity in the
central nervous system of vertebrates. Electrophysiological recordings of
single channels stimulated with agonists showed that both recombinant and
native AMPA receptors visit multiple conductance states in an agonist
concentration dependent manner. We propose an allosteric model of the multiple
conductance states based on concerted conformational transitions of the four
subunits, as an iris diaphragm. Our model predicts that the thermodynamic
behaviour of the conductance states upon full and partial agonist stimulations
can be described with increased affinity of receptors as they progress to
higher conductance states. The model also predicts existence of AMPA receptors
in non-liganded conductive substates. However, spontaneous openings probability
decreases with increasing conductances. Finally, we predict that the large
conductance states are stabilized within the rise phase of a whole-cell EPSC in
glutamatergic hippocampal neurons. Our model provides a mechanistic link
between ligand concentration and conductance states that can explain
thermodynamic and kinetic features of AMPA receptor gating.
