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.
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 IBa without modifying their voltage kinetics. This increased IBa could 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, omega-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open 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.
Llinás
R
R
Department of Physiology and Biophysics, New York University Medical Center, NY 10016.
Sugimori
M
M
Cherksey
B D
BD
Smith
R G
RG
Delbono
O
O
Stefani
E
E
Appel
S
S
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000276:immunology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002525:Cerebellar Cortex / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D011073:Polyamines / Q000633:toxicity; D011689:Purkinje Cells / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; C071920:FTX, spider toxin; D007074:Immunoglobulin G; D008051:Lipid Bilayers; D009498:Neurotoxins; D011073:Polyamines; D013779:Tetrodotoxin