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Publication of the Year 2005

C. Schmidt, M. Werner, and M. Hollmann (2006).
Revisiting the postulated “unitary glutamate receptor”: Electrophysiological and pharmacological analysis in two heterologous expression systems fails to detect any evidence for its existence.
Molecular Pharmacology 69(1): 119-129.
Published online in October 2005.
doi: 10.1124/mol.105.016840
Abstract

In 1996 the group of Eric Barnard published the contentious hypothesis that a so-called “unitary glutamate receptor” existed that united the electrophysiological and pharmacological properties of all three classical glutamate receptor subfamilies. As this receptor was reported to consist of the Xenopus NMDA receptor subunit XenNR1-4b and the Xenopus kainate binding protein XenU1, we cloned both cDNAs in an effort to reproduce and verify the postulated special ion channel properties. To this end we coexpressed the two proteins in HEK cells as well as Xenopus oocytes and analysed the resulting ion channels. We found that both proteins are expressed and are colocalized in the plasma membrane. However, no ionic currents beyond those elicited by glutamate/glycine also at the homomeric XenNR1-4b subunit alone could be detected. In particular, none of the reported unusual AMPA-or kainate-induced currents were ever seen. We conclude that the postulated “unitary glutamate receptor” does not exist, and that the published reports probably were based on experimental artifacts.