Ion pore properties of ionotropic glutamate receptors are modulated by a transplanted potassium channel selectivity filter.
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.
Hoffmann
Jutta
J
Dept. of Biochemistry I-Receptor Biochemistry, Ruhr University Bochum, Building NC, Level 6, Rm. 170, D-44787 Bochum, Germany.
Gorodetskaia
Anna
A
Hollmann
Michael
M
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
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