Basile A S, Koustova E, Ioan P, Rizzoli S, Rogawski M A, Usherwood P N
Laboratory of Bioorganic Chemistry, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Neurobiol Dis. 2001 Dec;8(6):1069-81. doi: 10.1006/nbdi.2001.0442.
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.
生物化学和免疫学研究表明，感染LP - BM5病毒的小鼠会产生针对离子型谷氨酸受体的抗体。在此，从感染小鼠大脑中分离出的IgG已在培养的大鼠皮质和海马神经元上进行了电生理测试。该IgG引发了不依赖甘氨酸的电流，其反转电位约为0 mV。来自未感染小鼠的同等浓度的IgG无活性。与AMPA和KA引发的电流相比，不依赖甘氨酸的电流受DNQX和GYKI - 52466的影响较小。该IgG还引发了依赖甘氨酸的电流，其反转电位为 - 10 mV，并被dl - AP5、5,7 - DCKA和多胺酰胺阻断。依赖甘氨酸和不依赖甘氨酸的电流不受河豚毒素、士的宁、跨膜Cl-梯度或d - 筒箭毒碱的影响。尽管部分不依赖甘氨酸的电流仍未明确，但这些结果证实，病毒诱导的免疫病理学产生了激活离子型谷氨酸受体的IgG克隆，从而可能导致在感染LP - BM5的小鼠中观察到的兴奋性毒性神经综合征。
