title: A relative weak leg muscle in the rolling Nagoya mouse as a model for Lambert-Eaton myasthenic syndrome.
abstract: The Lambert-Eaton myasthenic syndrome (LEMS) is caused by auto-antibodies that affect the activity of presynaptic calcium channels at the neuromuscular junction. Weakness in LEMS is particularly affecting the legs. Here we used leg muscles from the rolling Nagoya (RN) mouse with a R1262G mutation in the alpha-1 subunit of the P/Q-type (Ca(v)2.1) calcium channel. We found that in homozygote flexor digitorum brevis (FDB) muscles the contractions by single pulses, expressed as relative to contractions by direct stimulation, were smaller (43%) than in controls (94%) with 0.5 mM Ca(2+) in the medium. In both homozygote RN and control animals the contractions of the FDB by single pulses were affected more than the corresponding contractions of the diaphragm; RN muscles with 0.5 mM Ca(2+), FDB 42% and Dia 91%, respectively; control muscles with 0.25 mM Ca(2+), FDB 9% and Dia 39%, respectively. At 40 Hz stimulation this difference was 35% and 76% with 0.35 mM Ca(2+). In RN and control mice both muscles were about equally sensitive to 200 and 400 microM tubocurarine. The results suggest that leg weakness in LEMS may result from a relatively small safety factor of neuromuscular transmission and that this could become particularly prominent when the activity of calcium channels is diminished.
authors.affiliation: Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands. p.molenaar@np.unimaas.nl
authors.forename: P C
authors.initials: PC
authors.lastname: Molenaar
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics; D020907:Calcium Channels, Q-Type / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D006614:Hindlimb; D066298:In Vitro Techniques; D015624:Lambert-Eaton Myasthenic Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology*; D009154:Mutation; D009469:Neuromuscular Junction / Q000503:physiopathology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D002118:Calcium; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018733:Nicotinic Antagonists; D014403:Tubocurarine