Block of recombinant nicotinic receptor channels by IgG from myasthenic patients.
In myasthenia gravis (MG), specific antibodies directed against nicotinic acetylcholine receptor (nAChR) channels are produced. Recently, a distinct blockade of native embryonic-type nAChR channels by purified IgG from MG patients has been demonstrated. In the present study, we investigated the interaction of myasthenic IgG with recombinant embryonic- or adult-type nAChR channels expressed on human embryonic kidney (HEK) 293 cells. For the experiments, the patch clamp technique was applied in combination with an ultra-fast application system for agonists. Repetitive 20-ms pulses of 1 mM acetylcholine (ACh) were applied with or without purified IgG added to the perfusion system. The purified IgG from MG patients blocked currents through both, embryonic- and adult-type nAChR channels to a similar extent. A block by myasthenic IgG of adult-type nAChR channels, which are present exclusively at the postsynaptic membrane of the neuromuscular synapse, was shown to occur. The reversible pharmacological blockade of adult-type nAChR channels by myasthenic IgG may be one factor responsible for rapid fluctuations of weakness or rapid recovery of muscle strength after plasmapheresis in MG.
Krampfl
Klaus
K
Department of Neurology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Dengler
Reinhard
R
Bufler
Johannes
J
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D011978:Receptors, Nicotinic; D000109:Acetylcholine