Anti-ganglio side antibodies alter presynaptic release and calcium influx

NEUROBIOLOGY OF DISEASE

卷:28

Article

Buchwald, Brigitte ; Zhang, Gang ; Vogt-Eisele, Angela K. ; Zhang, Weiyi ; Ahangari, Raheleh ; Griffin, John W. ; Hatt, Hanns ; Toyka, Klaus V. ; Sheikh, Kazim A.

关键词: Guillain-Barre syndrome;    AMAN;    anti-ganglioside antibodies;    gangliosides;    immune neuropathies;    neuromuscular junction;    calcium influx;   

DOI  :  10.1016/j.nbd.2007.07.008

来源: Elsevier

【 摘 要 】

Acute motor axonal neuropathy (AMAN) variant of Guillain-Barr syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1 a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti-gangliosde mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody-mediated muscle weakness in AMAN. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

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