Amyotrophic lateral sclerosis immunoglobulins are ineffective in altering calcium influx through presynaptic voltage-sensitive calcium channels.
Recent work has suggested that one factor in the etiology of the neuromuscular disease, amyotrophic lateral sclerosis (ALS), may be an autoimmune mechanism in which presynaptic voltage-sensitive calcium channels are an antigenic target. We have developed a fluorescence technique to measure rapid Ca2+ influx through presynaptic calcium channels in isolated nerve terminals (synaptosomes) from rat cerebral cortex. Depolarization of the synaptosomes by elevated external K+ concentration caused a rapid increase in cytoplasmic Ca2+, as measured by a change in fluorescence of the Ca2+ chelating dye, Fura-2, which was loaded inside the synaptosomes. Pharmacological characterization suggests that the P- and Q-subtypes of voltage-sensitive calcium channels mediate the majority of this Ca2+ influx. The synaptosome preparation has been used as a model system to investigate the effects of IgG, purified from eight ALS patients, on presynaptic calcium channel function. IgG (1 microgram ml-1 to 1 mg ml-1) was preincubated with the synaptosomes prior to depolarization. IgG, from these eight ALS patients, had no systematic effects on presynaptic Ca2+ influx. Thus, using this system, we find no evidence for an effect of ALS IgG on the function of presynaptic calcium channels.
Thomas
M M
MM
Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Dunn
S M
SM
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology*; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007074:Immunoglobulin G; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D002118:Calcium