Effects of IgG anti-GM1 monoclonal antibodies on neuromuscular transmission and calcium channel binding in rat neuromuscular junctions
Autor(es): Hotta Sayako,Nakatani Yoshihiko,Kambe Toshie,Abe Kenji,Masuda Yutaka,Utsumomiya Iku,Taguchi Kyoji
Resumo: Guillain-Barré syndrome is a type of acute inflammatory neuropathy that causes ataxia and is associated with the IgG anti-GM1 antibody. However, the pathogenic role of the IgG anti-GM1 antibody and calcium channels in neuromuscular junctions (NMJs) remains unclear. Thus, the aim of the present study was to investigate the effects of the IgG anti-GM1 monoclonal antibody (mAb) on spontaneous muscle action potentials (SMAPs), and the effects of calcium channel blockers, in a rat spinal cord-muscle co-culture system. In addition, the binding of IgG anti-GM1 mAb to calcium channels was investigated in the rat hemidiaphragm. The frequency of SMAPs in the innervated muscle cells was acutely inhibited by the IgG anti-GM1 mAb; however, this effect was blocked by the N-type calcium channel blocker, ?-conotoxin GVIA (30 nM). Furthermore, the P/Q-type calcium channel blocker, ?-agatoxin IVA (10 nM), was found to partially block the IgG anti-GM1 mAb-induced inhibitory effect in the spinal cord-muscle co-culture system. Immunohistochemical analysis of the rat hemidiaphragm indicated that IgG anti-GM1 mAb binding overlapped with anti-Cav2.2 (?1B) antibody binding in the nerve terminal. In addition, IgG anti-GM1 mAb binding partially overlapped with anti-Cav2.1 (?1A) antibody binding. Thus, the results demonstrated that the IgG anti-GM1 mAb binds to calcium channels in the nerve terminals of NMJs. Therefore, the inhibitory effect of IgG anti-GM1 mAb on SMAPs may involve N-type and P/Q-type calcium channels in motor nerve terminals at the NMJ.
Palavras-Chave: Guillain-Barré syndrome; IgG anti-GM1 monoclonal antibody; Calcium channel; Muscle action potential; Neuromuscular junctions
Imprenta: Experimental and Therapeutic Medicine, v. 10, n. 2, p. 535-540, 2015
Identificador do objeto digital: 10.3892/etm.2015.2575
Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Transmission
Data de publicação: 2015