Mechanism of block of nicotinic acetylcholine receptor channels by purified IgG from seropositive patients with myasthenia gravis

Citation
K. Jahn et al., Mechanism of block of nicotinic acetylcholine receptor channels by purified IgG from seropositive patients with myasthenia gravis, NEUROLOGY, 54(2), 2000, pp. 474-479
Citations number
20
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
NEUROLOGY
ISSN journal
00283878 → ACNP
Volume
54
Issue
2
Year of publication
2000
Pages
474 - 479
Database
ISI
SICI code
0028-3878(20000125)54:2<474:MOBONA>2.0.ZU;2-O
Abstract
Objective: To clarify the mechanism of block of nicotinic receptor channels by myasthenic antibodies. Background: Nicotinic acetylcholine receptor (nA ChR) channel currents are functionally blocked by purified immunoglobulin G (IgG) of patients with myasthenia gravis (MG). Methods: The molecular mech anism of block of IgG fractions containing antibodies to nAChR channels was tested with the patch-clamp technique in combination with a system for ult rafast solution exchange. For the experiments, outside-out patches from cul tured mouse myotubes that express embryonic-type nAChR channels at their su rface were used. Results: Incubation of outside-out patches with purified I gG from four myasthenic patients blocked nAChR channel currents activated b y the application of 1.0 mM ACh reversibly. The peak current amplitude and the time course of block of nAChR channels decreased with increasing concen trations of IgG. The block became at least partly irreversible if incubatio n time of outside-out patches exceeded 2 minutes. For the block of nAChR ch annel currents with alpha-bungarotoxin, a similar mechanism of block was fo und. Conclusions: The reversibility of functional block of nAChR channel cu rrents by myasthenic IgG depended strongly on the incubation time of the re ceptors with antibodies. Interaction of myasthenic antibodies with nicotini c receptors may proceed in several stages from a low-affinity reversible to a high-affinity irreversible binding. Key words: Myasthenia gravis-Block m echanism-Myasthenic antibodies-Immunoglobulin G-Patch-clamp technique-Ultra fast application-Nicotinic acetylcholine receptor.