"AMPA and kainate receptors mediate fast excitatory synaptic transmission. AMPA receptor ligand-binding domains form dimers, which are well-known to control ion channel activation and desensitization. The dimer stability is related to the rate and extent of desensitization. Despite the similarity in structure between AMPA and kainate receptors, they present a clear difference in function, suggesting that specific interactions governing gating differ between these two subtypes. In this application we propose a series of chemical, electrophysiological and structural experiments to find the structural determinants of desensitization on AMPA and kainate receptors. Based on hypotheses of the tetrameric arrangements of subunits, we will insert reactive amino acids in key sites on the channels. Using a unique multi barrel fast perfusion system, we will trap receptors in different configurations using transition metal bridges or disulphide bonds, to map the interactions between dimers and determine the conformational differences between these two receptors."
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