Fab fragments from amyotrophic lateral sclerosis IgG affect calcium channels of skeletal muscle

O. Delbono, V. Magnelli, T. Sawada, R. G. Smith, Stanley H. Appel, E. Stefani

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a human disease involving upper and lower motoneurons. In this paper we studied the action of specific antigen- binding site (Fab) fragments of immunoglobulins from ALS patients on dihydropyridine (DHP)-sensitive Ca2+ channel function in situ. Ca2+ channels in single mammalian skeletal muscle fibers tested by the double Vaseline gap technique and single Ca2+ channels reconstituted into bilayer were tested in these experiments. Although the observed current-voltage relationship was not modified by the addition of Fab fragments (1.5 mg/ml), peak Ca2+ current (I(Ca)) was significantly reduced. The effect of these Fab fragments on the peak I(Ca) reached a stable value after 60 min of incubation. ALS Fab fragments also slowed the I(Ca) rising phase and increased the rate of tail current deactivation. Studies with double pulses demonstrated that I(Ca) inactivation time course, voltage dependence, and recovery were not modified by ALS Fab fragments. Fab fragments from normal subjects and heat-inactivated Fab fragments from ALS patients did not induce any modification on the charge movement and I(Ca). In single channel studies, ALS Fab fragments reduced channels amplitude. These data support the concept of an immunological interaction between the circulating antibodies from ALS patients and DHP-sensitive Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)C537-C543
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3 33-3
StatePublished - 1993


  • excitation-contraction coupling
  • immunoglobulin G
  • mammalian skeletal muscle

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology


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