Fab fragments from amyotrophic lateral sclerosis IgG affect calcium channels of skeletal muscle
Delbono, O.; Magnelli, V.; Sawada, T.; Smith, R.G.; Appel, S.H.; Stefani, E.
American Journal of Physiology 264(3 Pt 1): C537-C543
1993
ISSN/ISBN: 0002-9513 PMID: 8384783 Document Number: 405454
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 Ca-2+ channel function in situ. Ca-2+ channels in single mammalian skeletal muscle fibers tested by the double Vaseline gap technique and single Ca-2+ 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 Ca-2+ 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 Ca-2+ channels.