Effects of IgG anti-GM1 monoclonal antibodies on neuromuscular transmission and calcium channel binding in rat neuromuscular junctions

Hotta,Sayako; Nakatani,Yoshihiko; Kambe,Toshie; Abe,Kenji; Masuda,Yutaka; Utsumomiya,Iku; Taguchi,Kyoji

doi:10.3892/etm.2015.2575

Effects of IgG anti-GM1 monoclonal antibodies on neuromuscular transmission and calcium channel binding in rat neuromuscular junctions

Authors:
- Sayako Hotta
- Yoshihiko Nakatani
- Toshie Kambe
- Kenji Abe
- Yutaka Masuda
- Iku Utsumomiya
- Kyoji Taguchi
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Affiliations: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194‑8543, Japan, Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194‑8543, Japan, Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963‑8611, Japan, Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Machida, Tokyo 194‑8543, Japan, Department of Developmental Education, Showa Pharmaceutical University, Machida, Tokyo 194‑8543, Japan
Published online on: June 12, 2015 https://doi.org/10.3892/etm.2015.2575
Pages: 535-540

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Abstract

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, ω‑conotoxin GVIA (30 nM). Furthermore, the P/Q‑type calcium channel blocker, ω‑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 (α1B) antibody binding in the nerve terminal. In addition, IgG anti‑GM1 mAb binding partially overlapped with anti‑Cav2.1 (α1A) 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.

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