title: Beauvericin Inhibits Neuromuscular Transmission and Skeletal Muscle Contractility in Mouse Hemidiaphragm Preparation.
abstract: The effects of Beauvericin (BEA) produced by the fungusBeauveria bassianaandFusariumsp. on neuromuscular transmission and contractility were determined in an isolated neuromuscular mouse hemidiaphragm preparation. BEA (5 µM) significantly inhibits indirectly elicited twitch amplitude. At higher concentrations (7.5 and 10 µM), BEA produces a significant reduction of directly elicited, or complete block of indirectly evoked, muscle contraction. BEA also appears to be myotoxic, as indicated by a slowly developing muscle contracture. Development of neuromuscular blockade and contracture is concentration dependent. BEA acted by presynaptically depressing spontaneous acetylcholine release as indicated by the reduction in the frequency of spontaneous miniature endplate potentials (MEPPs), while the membrane potential of muscle fibers remained unchanged. At higher concentrations (7.5 and 10 µM), BEA progressively reduces or completely blocks MEPPs and EPPs amplitudes. Changes in MEPPs and EPPs are associated with substantial depolarization of muscle fibers when exposed to 7.5 and 10 µM of BEA. These results indicate that BEA has neurotoxic and myotoxic effects, which overlap in a narrow range of concentrations.
authors.affiliation: *Institute for physiology, pharmacology and toxicology, Veterinary faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia; and.
authors.forename: Monika Cecilija
authors.initials: MC
authors.lastname: Žužek
authors.affiliation: Institute for hygiene and pathology of animal nutrition, Veterinary faculty, University of Ljubljana, Cesta v Mestni log 47, 1000 Ljubljana, Slovenia.
authors.forename: Marjana
authors.initials: M
authors.lastname: Grandič
authors.affiliation: Institute for hygiene and pathology of animal nutrition, Veterinary faculty, University of Ljubljana, Cesta v Mestni log 47, 1000 Ljubljana, Slovenia.
authors.forename: Breda
authors.initials: B
authors.lastname: Jakovac Strajn
authors.affiliation: *Institute for physiology, pharmacology and toxicology, Veterinary faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia; and robert.frangez@vf.uni-lj.si.
authors.forename: Robert
authors.initials: R
authors.lastname: Frangež
mesh_terms: D000818:Animals; D047630:Depsipeptides / Q000302:isolation & purification / Q000633:toxicity*; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D047630:Depsipeptides; C004456:beauvericin
keywords: beauvericin; motor endplate; mouse; muscle contractility; neuromuscular transmission