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  • 标题:Human autoantibodies specific for the α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons
  • 本地全文:下载
  • 作者:Ashwin Pinto ; Samantha Gillard ; Fraser Moss
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1998
  • 卷号:95
  • 期号:14
  • 页码:8328-8333
  • DOI:10.1073/pnas.95.14.8328
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the 1 pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same 1 gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K+-stimulated [Ca2+]i increase in the 1A cell line but not in the 1B, 1C, 1D, and 1E cell lines, establishing the 1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the 1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.
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