title: Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.
abstract: Although considerable progress has been made in characterizing the physiological function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1- or KA2-containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non-functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and KA receptors.
authors: Institute for Biochemistry, Emil-Fischer-Center, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany.
authors: Carmen
authors: C
authors: Villmann
authors: Jutta
authors: J
authors: Hoffmann
authors: Markus
authors: M
authors: Werner
authors: Sabine
authors: S
authors: Kott
authors: Nathalie
authors: N
authors: Strutz-Seebohm
authors: Tanja
authors: T
authors: Nilsson
authors: Michael
authors: M
authors: Hollmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016296:Mutagenesis / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D014982:Xenopus laevis
chemical_list: D002118:Calcium; D016291:Dizocilpine Maleate; D018683:Excitatory Amino Acid Agents; D007473:Ion Channels; D007608:Kainic Acid; D009498:Neurotoxins; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins