title: IgM anti-GQ1b monoclonal antibody inhibits voltage-dependent calcium current in cerebellar granule cells.
abstract: Miller-Fisher syndrome (MFS), which is known to be associated with anti-GQ1b antibodies and to cause ataxia, is a variant of an acute inflammatory neuropathy. However, the pathogenic role of anti-GQ1b antibodies remains unclear. In this study, we investigated the effects of mouse IgM anti-GQ1b monoclonal antibody (IgM anti-GQ1b mAb) on the spontaneous muscle action potential of a rat spinal cord-muscle co-culture system and on the voltage-dependent calcium channel (VDCC) current in cerebellar granule cells and Purkinje cells using the whole-cell patch clamp technique. The frequency of spontaneous muscle action potential of the innervated muscle cells was transiently increased by IgM anti-GQ1b mAb and then was blocked completely, which was the same finding as reported previously. Moreover, the cerebellar granule cell VDCC current was decreased by 30.76+/-7.60% by 5 microg/mL IgM anti-GQ1b mAb, whereas IgM anti-GQ1b mAb did not affect the VDCC current in cerebellar Purkinje cells. In immunocytochemistry, IgM anti-GQ1b mAb stained the whole cell surface of cerebellar granule cells, but not that of Purkinje cells. Therefore, the clinical symptoms of Miller-Fisher syndrome, such as cerebellar-like ataxia, may be explained by the inhibitory effects of anti-GQ1b antibodies on VDCC current in cerebellar granule cells.
authors.affiliation: Department of Pharmacotherapeutics, Showa Pharmaceutical University, Machida, Tokyo 195-8543, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Mikio
authors.initials: M
authors.lastname: Murata
authors.forename: Keiko
authors.initials: K
authors.lastname: Shibata
authors.forename: Takumi
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Iku
authors.initials: I
authors.lastname: Utsunomiya
authors.forename: Seigo
authors.initials: S
authors.lastname: Usuki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Miyatake
authors.forename: Keiko
authors.initials: K
authors.lastname: Hoshi
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D005732:Gangliosides / Q000276:immunology*; D007075:Immunoglobulin M / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000276:immunology; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D019846:Miller Fisher Syndrome / Q000276:immunology / Q000503:physiopathology; D009046:Motor Neurons / Q000187:drug effects / Q000276:immunology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000294:innervation; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001323:Autoantibodies; D015220:Calcium Channels; D005732:Gangliosides; D007075:Immunoglobulin M; C039129:GQ1b ganglioside