NON-DESENSITIZING AMPA-RECEPTORS

摘要

The present invention relates to a nucleic acid molecule encoding a (poly)peptide which has an amino acid sequence of a glutamate receptor of the AMPA-type and functions as a non-desensitizing AMPA-receptor or as a non-desensitizing subunit thereof, wherein the leucine corresponding to position 497 of the wildtype rat AMPA-receptor GluR1flip or the leucine at the position which corresponds in other glutamate receptors of the AMPA-type by comparison of homology to position 497 of the wildtype rat AMPA-receptor GluR1flip is replaced by an aromatic amino acid. The invention further relates to (poly)peptides encoded by said nucleic acid molecules, vectors and hosts comprising said nucleic acid molecules, as well as to methods for producing (poly)peptides encoded by said nucleic acid molecules. The present invention also provides for antibodies specifically directed to (poly)peptides encoded by said nucleic acid molecules. Additionally, the invention relates to a method for the blocking of desensitization of a glutamate receptor of the AMPA-type, comprising the step of replacing a leucine which corresponds by comparison of homology to position 497 of the rat AMPA-receptor GluR1 by an aromatic amino acid and methods for identifying and/or characterizing molecules which are capable of interaction with glutamate receptors of the AMPA type. The invention also relates to the one of the aforementioned nucleic acid molecules, (poly)peptides, hosts, vectors and/or antibodies as biosensors, for the characterization of glutamate receptor channel properties and/or for the preparation of pharmaceutical compositions. Furthermore, the invention provides for pharmaceutical compositions, diagnostics and kits comprising and/or employing the compounds of the invention.