IgG isolated from LP-BM5 infected mouse brain activates ionotropic glutamate receptors.
Biochemical and immunological studies have shown that mice infected with LP-BM5 virus develop antibodies to ionotropic glutamate receptors. Here, IgG isolated from brain of infected mice has been tested electrophysiologically on cultured rat cortical and hippocampal neurons. The IgG elicited glycine-independent currents that reversed at approximately 0 mV. Equivalent concentrations of IgG from uninfected mice were inactive. The glycine-independent currents were less influenced by DNQX and GYKI-52466 than currents elicited by AMPA and KA. The IgG also elicited glycine-dependent currents that reversed at -10 mV and were blocked by dl-AP5, 5,7-DCKA, and polyamine amides. Glycine-dependent and -independent currents were unaffected by tetrodotoxin, strychnine, the transmembrane Cl- gradient or d-tubocurare. Although part of the glycine-independent current remains uncharacterized, these results confirm that a virus-induced immunopathology produces IgG clones that activate ionotropic glutamate receptors and that could, thereby, contribute to the excitotoxic neurological syndrome observed in LP-BM5-infected mice.
Basile
A S
AS
Laboratory of Bioorganic Chemistry, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Koustova
E
E
Ioan
P
P
Rizzoli
S
S
Rogawski
M A
MA
Usherwood
P N
PN
D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000821:virology; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D029122:Murine pneumonia virus / Q000276:immunology* / Q000472:pathogenicity; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology
D001323:Autoantibodies; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007074:Immunoglobulin G; D018733:Nicotinic Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine; D014403:Tubocurarine