IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-12, Vol.90 (24), p.11743-11747
• Main Authors: Llinas, R., Sugimori, M., Cherksey, B. D., Smith, R. Glenn, Delbono, O., Stefani, E., Appel, S.
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - immunology; Animals; Barium; Biological and medical sciences; Calcium; Calcium Channels - drug effects; Calcium Channels - physiology; Cellular biology; Cerebellar Cortex - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electric current; Electric potential; Gels; Guinea Pigs; Humans; Immunoglobulin G - blood; Immunoglobulin G - isolation & purification; Immunoglobulin G - pharmacology; In Vitro Techniques; Lipid Bilayers; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurological disorders; Neurology; Neurotoxins - toxicity; P type calcium channels; Polyamines - toxicity; Purkinje cells; Purkinje Cells - physiology; Tetrodotoxin - pharmacology; Toxins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.24.11743

The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBawithout modifying their voltage kinetics. This increased IBacould be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, ω-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBaopen time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.