title: Lack of effect of Miller Fisher sera/plasmas on transmitter release from PC12 cells.
abstract: IgG antibodies to GQ1b ganglioside are found in > 90% of patients with the Miller Fisher Syndrome (MFS). MFS sera or IgG preparations have marked effects on neurotransmitter release at the neuromuscular junction, but their mode(s) of action remain unclear. To establish a cell-based system for investigating the mechanism of action of MFS serum preparations, we looked at neurotransmitter release from three cell lines. We failed to demonstrate substantial 14C-acetylcholine release from two motor-neuronal cell lines, VSC4.1 and NSC19, and therefore studied 3H-noradrenaline release from NGF-differentiated PC12 cells, a neural-crest derived catecholaminergic cell line. K(+)-induced release was inhibited by botulinum toxin and basal release was enhanced by alpha-latrotoxin, resembling that at the neuromuscular junction, although K(+)-induced release was dependent on L-type rather than P/Q-type calcium channels. The cells expressed polysialylated gangliosides on the cell surface. Incubation in heat-inactivated or untreated MFS preparations did not, however, affect basal or K(+)-induced release. Thus the PC12 cells do not appear to be sensitive to the effects of serum antibodies from MFS patients.
authors.affiliation: Institute of Molecular Medicine, University of Oxford, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Benatar
authors.forename: H J
authors.initials: HJ
authors.lastname: Willison
authors.forename: A
authors.initials: A
authors.lastname: Vincent
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005732:Gangliosides / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D006822:Hybrid Cells; D007106:Immune Sera / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D051379:Mice; D019846:Miller Fisher Syndrome / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009447:Neuroblastoma; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D013116:Spinal Cord; D014407:Tumor Cells, Cultured
chemical_list: D005732:Gangliosides; D007106:Immune Sera; D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; C039129:GQ1b ganglioside