Concentration-dependent substrate behavior of native AMPA receptors

AMPA-type glutamate receptors mediate most excitatory postsynaptic currents (EPSCs) at central synapses, and their conductance determines in part the size of EPSCs. The conductance of a recombinant AMPA receptor depends on th e number of agonist molecules bound to the channel. Here we tested whether native AMPA and kainate receptors show this behavior in outside-out patches from neurons in situ by measuring conductance levels of single channels ov er a wide range of agonist concentrations. We found that the conductance of AMPA, but not kainate, receptors depended strongly on agonist concentratio n. Our results suggest that alterations in the glutamate concentration in t he synaptic cleft may change the apparent unitary conductance of postsynapt ic AMPA receptors.