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. Amyotrophic lateral sclerosis (ALS) is the most common human motor neuron disease. Affected individuals show progressive dysfunction and degeneration of brain, brainstem, and spinal cord motor neurons, clinically manifested as progressive muscular weakness, paralysis, and death within a mean of 3 years. 35 There is no cure available for this disease and its pathophysiology remains unclear.Electrophysiological studies of muscle biopsies from ALS patients have revealed severe presynaptic impairment of neuromuscular transmission. 16 In addition, some endplates show signs of immaturity, in accordance with the process of degeneration and regeneration known to occur in this disease.
25There is general agreement that the selective death of motoneurons results from a cascade of toxic biological events triggered by a variety of factors. ALS can be considered a multifactorial disorder that includes a population of genetically predisposed patients. Sporadic ALS accounts for approximately 90% of reported cases and familial cases constitute 5-10%. 5,27,28 In sporadic ALS patients, motoneuron
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