Rinsho Shinkeigaku (Clinical Neurology)

The 50th Annual Meeting of the Japanese Society of Neurology

Recent advance in research for myasthenia gravis, in relation to various antibodies affecting synaptic structure and function

Masaharu Takamori, M.D.

Neurological Center, Kanazawa-Nishi Hospital

Autoantibodies impair acetylcholine receptor (AChR) in myasthenia gravis (MG) and P/Q-type voltage-gated calcium channel (VGCC) in Lambert-Eaton myasthenic syndrome (LEMS). (1) Some of MG and LEMS patients are "seronegative" for respective antibodies or modified by antibodies that recognize other proteins than AChR and VGCC such as MuSK, AChR allosteric site, membrane Na+ channel and ryanodine receptor-1 (RyR1) in MG, and synaptotagmin-1 in LEMS. (2) Autoimmune responses affect the proteins participating in the mechanisms to compensate for synaptic disorders on the basis of presynaptic Ca2+ homeostasis provided by VGCC and non-VGCC (receptor-operated TRPCs); they act as enhancers of Ca2+-mediated ACh release via phospholipase C signaling pathways including M1-type presynaptic muscarinic AChR, neurotrophin receptor (TrkB), and fast-mode of synaptic vesicle recycling. (3) The pathophysiology contributive to contractile fatigue in MG includes RyR1 and also TRPC3. The TRPC3 also forms a complex with STIM1 and Orai1 to make up for Ca2+ after sarcoplasmic Ca2+ release. The prevalent detection of anti-TRPC3 antibodies in MG with thymoma could affect muscle contractile machineries in addition to anti-RyR1-induced affection. (4) When one faces "seronegative" MG, one should be cautious to conformation-specific antibodies and also congenital myasthenic syndromes.
Full Text of this Article in Japanese PDF (561K)

(CLINICA NEUROL, 49: 789|793, 2009)
key words: nicotinic and muscarinic acetylcholine receptors, voltage-gated and non-voltage-gated calcium channels, synaptotagmin, ryanodine receptor, conformation-specific antibodies

(Received: 22-May-09)