Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Fumiharu Kimura, R. Glenn Smith, Osvaldo Delbono, Okot Nyormoi, Toni Schneider, Wolfgang Nastainczyk, Franz Hofmann, Enrico Stefani, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis possess immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti-voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore-forming α1 subunit of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α1 subunit-directed monoclonal antibody, which itself mimics the effects of ALS IgG on skelatal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α1 and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalAnnals of Neurology
Issue number2
StatePublished - Feb 1994

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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