Beauvericin inhibits neuromuscular transmission and skeletal muscle contractility in mouse hemidiaphragm preparation

Abstract

The effects of Beauvericin (BEA) produced by the fungus Beauveria bassiana and Fusarium sp. 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.