title: The N-methyl-D-aspartate receptor's neglected subunit - GluN1 matters under normal and hyperbaric conditions.
abstract: Professional deep-water divers exposed to hyperbaric pressure (HP) above 1.1 MPa develop high-pressure neurological syndrome, which is associated with central nervous system hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible neuronal damage. In addition, we have reported that HP (10.1 MPa) differentially affects ionic currents, measured by the two-electrode voltage-clamp technique, of eight specific NMDAR subtypes generated by the co-expression of GluN1-1a or GluN1-1b with one of the four GluN2(A-D) subunits in Xenopus laevis oocytes. We now report that eight GluN1 splice variants, when co-expressed with GluN2A, mediate different ionic currents at normal and HP (5.1 MPa). These data, in conjunction with our previous results, indicate that both GluN1 and GluN2 subunits play a critical role in determining NMDAR currents under normal and HP conditions. These data, given the differential spatial distribution of the different NMDAR subtypes in the central nervous system, may offer a partial explanation for the mechanism governing the complex signs and symptoms of high-pressure neurological syndrome, and an explanation for the suspected long-term HP health decrement due to repetitive deep dives by professional divers.
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel.
authors.forename: Alice
authors.initials: A
authors.lastname: Bliznyuk
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Aviner
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel.
authors.forename: Hava
authors.initials: H
authors.lastname: Golan
authors.affiliation: Department of Biochemistry I, Receptor Biochemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hollmann
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, Beer-Sheva, 84105, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Grossman
mesh_terms: D000818:Animals; D006610:High Pressure Neurological Syndrome / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes; D011312:Pressure / Q000009:adverse effects; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Xenopus laevis; central nervous system hyperexcitability; diving physiology; high-pressure neurological syndrome; oocyte; pressure