Concentration-dependent substate behavior of native AMPA receptors

Abstract

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 the 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 over a wide range of agonist concentrations. We found that the conductance of AMPA, but not kainate, receptors depended strongly on agonist concentration. Our results suggest that alterations in the glutamate concentration in the synaptic cleft may change the apparent unitary conductance of postsynaptic AMPA receptors.

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Figure 1: Activity of a larger-conductance AMPA receptor over a wide range of agonist concentrations.
Figure 2: Activity of a smaller-conductance AMPA receptor over a wide range of agonist concentrations.
Figure 3: AMPA receptors spend more time in smaller conductance levels in the presence of the competitive antagonist NBQX.
Figure 4: Single-channel activity of a kainate receptor at three concentrations of domoate.
Figure 5: The effect of agonist concentration on the single-channel conductance of native AMPA and kainate receptors.

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Acknowledgements

This work was supported by an NIH grant (GM58926) to J.R.H.

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Correspondence to James R. Howe.

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Smith, T., Howe, J. Concentration-dependent substate behavior of native AMPA receptors. Nat Neurosci 3, 992–997 (2000). https://doi.org/10.1038/79931

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