1. Anti-ganglioside antibodies alter presynaptic release and calcium influx
- Author
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Buchwald, Brigitte, Zhang, Gang, Vogt-Eisele, Angela K., Zhang, Weiyi, Ahangari, Raheleh, Griffin, John W., Hatt, Hanns, Toyka, Klaus V., and Sheikh, Kazim A.
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ALTERNATIVE medicine , *IMMUNOGLOBULINS , *NEUROPATHY , *IMMUNOGLOBULIN G - Abstract
Abstract: Acute motor axonal neuropathy (AMAN) variant of Guillain–Barré 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 -GD1a 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. [Copyright &y& Elsevier]
- Published
- 2007
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