Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker.
In order to search for early changes induced by the application of human immunoglobulin G (IgG) on motor nerve terminals, IgG from patients with amyotrophic lateral sclerosis (ALS) and control subjects was injected subcutaneously into the levator auris muscle of mice. A week or a month after the last injection, endplate potentials were recorded. No changes in quantal content of transmitter release were observed. In control and ALS IgG-treated muscles, neurotransmitter release remained sensitive to P/Q-type and insensitive to N-type voltage-sensitive calcium channel (VSCC) blockers as in untreated muscles. In contrast, IgG from 5 of 8 different ALS patients induced a significant reduction in quantal content of the evoked response after incubation with nitrendipine, indicating that a novel sensitivity to this calcium channel blocker appears in these motor nerve terminals. These results indicate that ALS IgG induces plastic changes at nerve terminals. The expression of transmitter release coupled to L-type VSCC indicate that ALS IgGs are capable of inducing plastic changes at the nerve terminals that may participate in the process leading to neuronal death.
Fratantoni
S A
SA
Instituto de Biología Celular y Neurociencias Profesor Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Weisz
G
G
Pardal
A M
AM
Reisin
R C
RC
Uchitel
O D
OD
D000328:Adult; D000368:Aged; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000276:immunology*; D018482:Muscle, Skeletal / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009568:Nitrendipine / Q000494:pharmacology; D012016:Reference Values; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007074:Immunoglobulin G; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine