title: Effects of IgG anti-GM1 monoclonal antibodies on neuromuscular transmission and calcium channel binding in rat neuromuscular junctions.
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.
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Sayako
authors.initials: S
authors.lastname: Hotta
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Kambe
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Developmental Education, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Iku
authors.initials: I
authors.lastname: Utsumomiya
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
keywords: Guillain-Barré syndrome; IgG anti-GM1 monoclonal antibody; calcium channel; muscle action potential; neuromuscular junctions