title: The effect of plasma from muscle-specific tyrosine kinase myasthenia patients on regenerating endplates.
abstract: Muscle-specific tyrosine kinase (MuSK) is essential for clustering of acetylcholine receptors (AChRs) at embryogenesis and likely also important for maintaining synaptic structure in adult muscle. In 5 to 7% of myasthenia gravis (MG) cases, the patients' blood contains antibodies to MuSK. To investigate the effect of MuSK-MG antibody on synapse regeneration, notexin was used to induce damage to the flexor digitorum brevis muscle. We administered aliquots of MuSK-MG patients' plasma to the flexor digitorum brevis twice daily for a period up to 21 days, and muscles were investigated ex vivo in contraction experiments. AChR levels were measured with (125)I-alpha-bungarotoxin, and endplates were studied with quantitative immunohistochemistry. In normal muscles and in 14-day regenerated muscles, MuSK plasma caused impairment of nerve stimulus-induced contraction in the presence of 0.35 and 0.5 mmol/L Ca(2+) with or without 100 to 400 nmol/L tubocurarine. Endplate size was decreased in regenerated muscles relative to controls; however, we did not observe such differences in muscle not treated with notexin. MuSK plasma had no effect on the amount and turnover rate of AChRs. Our results suggest that anti-MuSK antibodies influence the activity of MuSK molecules without reducing their number, thereby diminishing the size of the endplate and affecting the functioning of AChRs.
authors.affiliation: Neurophysiology Section, Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: W Pascale
authors.initials: WP
authors.lastname: ter Beek
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Martínez
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
authors.forename: Marc H
authors.initials: MH
authors.lastname: de Baets
authors.forename: Axel R
authors.initials: AR
authors.lastname: Wintzen
authors.forename: Jan J G M
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: Erik H
authors.initials: EH
authors.lastname: Niks
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.forename: Peter C
authors.initials: PC
authors.lastname: Molenaar
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008954:Models, Biological; D009045:Motor Endplate / Q000187:drug effects / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009157:Myasthenia Gravis / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D010949:Plasma; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D011950:Receptors, Cholinergic / Q000097:blood* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D004546:Elapid Venoms; D011950:Receptors, Cholinergic; C005082:notexin; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium; D014403:Tubocurarine