title: Ion pore properties of ionotropic glutamate receptors are modulated by a transplanted potassium channel selectivity filter.
abstract: The canonical potassium channel selectivity filter motif TVGYG was transplanted into ionotropic glutamate receptors (iGluRs) of the AMPA and NMDA subtype to test whether it renders the iGluRs K(+) selective. The TVGYG motif modulated several ion pore properties of AMPA receptor as well as NMDA receptor mutants, e.g., the intra- and extracellular polyamine block, current/voltage relationships, open channel block by MK801 and Mg(2+), and permeability for divalent cations. However, introduction of the selectivity filter failed to increase the K(+) selectivity of homomeric AMPA and heteromeric NMDA receptor complexes, which may be due to absence of selectivity filter-stabilizing interaction sites in the iGluR pore domain. Our findings indicate that even if glutamate receptors appear to have the intrinsic capacity for K(+) permeability, as is demonstrated by the prokaryotic, glutamate-gated, K(+) selective GluR0, the isolated selectivity filter is not able to confer K(+) permeability to the relatively unselective iGluR cation pore.
authors.affiliation: Dept. of Biochemistry I-Receptor Biochemistry, Ruhr University Bochum, Building NC, Level 6, Rm. 170, D-44787 Bochum, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Anna
authors.initials: A
authors.lastname: Gorodetskaia
authors.forename: Michael
authors.initials: M
authors.lastname: Hollmann
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008845:Microinjections / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D014982:Xenopus laevis
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D024683:Potassium Channels, Tandem Pore Domain; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008274:Magnesium