RGD Reference Report - Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic disorders. - Rat Genome Database

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Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic disorders.

Authors: Takamori, M  Motomura, M  Fukudome, T  Yoshikawa, H 
Citation: Takamori M, etal., Eur J Neurol. 2007 Nov;14(11):1230-5. Epub 2007 Aug 31.
RGD ID: 5133415
Pubmed: PMID:17764462   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1468-1331.2007.01931.x   (Journal Full-text)

The Lambert-Eaton myasthenic syndrome (LEMS), often associated with small-cell lung carcinoma (SCLC), is a disorder of acetylcholine (ACh) release from motor nerve terminals. In most patients, it is caused by autoantibodies against the P/Q-type voltage-gated calcium channels (VGCC) that trigger ACh release. However, these antibodies are not detected in approximately 15% of clinically and electrophysiologically typical cases. The M1-type pre-synaptic muscarinic ACh receptor (M1 mAChR) modulates cholinergic neuromuscular transmission by linking to P/Q-type VGCC, and may partially compensate for the reduced calcium entry. Immunoblotting against solubilized human M1 mAChR, we detected autoantibodies in: (a) 14 of 20 (70%) anti-VGCC-positive LEMS patients; (b) all five anti-VGCC-negative LEMS patients, one of whose serum had previously passively transferred LEMS-type electrophysiological defects to mice; (c) all five LEMS patients with autonomic symptoms; (d) seven of 25 (28%) myasthenia gravis (MG) patients in whom increased ACh release partially compensates for post-synaptic defects; (e) none of 10 SCLC patients without LEMS. Although not proving primary pathogenicity of anti-M1 mAChR antibodies, the present results highlight their potential to affect synaptic compensatory mechanisms, more in LEMS than MG.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Chrm1  (cholinergic receptor, muscarinic 1)

Genes (Mus musculus)
Chrm1  (cholinergic receptor, muscarinic 1, CNS)

Genes (Homo sapiens)
CHRM1  (cholinergic receptor muscarinic 1)


Additional Information