Cytotoxicity of immunoglobulins from amyotrophic lateral sclerosis patients on a hybrid motoneuron cell line

R. Glenn Smith, Maria E. Alexianu, Garrett Crawford, Okot Nyormoi, Enrico Stefanii, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Patients with amyotrophic lateral sclerosis possess antibodies (ALS IgGs) that bind to L-type skeletal muscle voltage-gated calcium channels (VGCCs) and inhibit L-type calcium current. To determine whether interaction of ALS IgGs with neuronal VGCCs might influence motoneuron survival, we used a motoneuron-neuroblastoma hybrid (VSC 4.1) cell line expressing binding sites for inhibitors of L-, N-, and P-type VGCCs. Using direct viable cell counts, quantitation of propidium iodide- and fluorescein diacetate-labeled cells, and lactate dehydrogenase release to assess cell survival, we document that ALS IgG kills 40-70% of cAMP-differentiated VSC 4.1 cells within 2 days. ALS IgG-mediated cytotoxicity is dependent on extracellular calcium and is prevented by peptide antagonists of N- or P-type VGCCs but not by dihydropyridine modulators of L-type VGCCs. Preincubating IgG with purified intact L-type VGCC or with isolated VGCC α1 subunit also blocks ALS IgG- mediated cytotoxicity. These results suggest that ALS IgG may directly lead to motoneuron cell death by a mechanism requiring extracellular calcium and mediated by neuronal-type calcium channels.

Original languageEnglish (US)
Pages (from-to)3393-3397
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Apr 12 1994


  • autoimmune
  • calcium channel
  • cell death

ASJC Scopus subject areas

  • Genetics
  • General


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