Abstract

The kinetics of ligand gated ion channels are tuned to permit diverse roles in cellular signaling. To follow high-frequency excitatory synaptic input, postsynaptic AMPA-type glutamate receptors must recover rapidly from desensitization. Chimeras between AMPA and the related kainate receptors demonstrate that the ligand binding domains alone control the lifetime of the desensitized state. Mutation of nonconserved amino acids in the lower lobe (domain 2) of the ligand binding domain conferred slow recovery from desensitization on AMPA receptors, and fast recovery on kainate receptors. Single-channel recordings and a correlation between the rate of deactivation and the rate of recovery across panels of mutant receptors revealed that domain 2 also controls ion channel gating. Our results demonstrate that the same mechanism that ensures fast recovery also sharpens the response of AMPA channels to synaptically released glutamate.

Links

Publisher Full Text

Authors

Carbone AL, Plested AJ

Institution

Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.

Source

Neuron 74:5 2012 Jun 7 pg 845-57

MeSH

Amino Acids
Binding Sites
Biophysical Phenomena
Cell Line, Transformed
Electric Stimulation
Glutamic Acid
Humans
Ion Channel Gating
Kinetics
Ligands
Models, Molecular
Mutation
Patch-Clamp Techniques
Protein Binding
Protein Processing, Post-Translational
Protein Structure, Quaternary
Receptors, Glutamate
Time Factors
Transfection

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22681689