The effect of the Fusarium metabolite beauvericin on electromechanical and-physiological properties in isolated smooth and heart muscle preparationsof guinea pigs

The electromechanical and -physiological effects of beauvericin were studie d in isolated smooth and heart muscle preparations of the guinea pig. Beauv ericin concentration-dependently decreased the force of contraction in prec ontracted (60 mM KCl) terminal ilea with an IC50 of 0.86 muM, and in electr ically stimulated (1 Hz) papillary muscles with an IC50 of 18 muM. This neg ative inotropic effect in papillary muscles was antagonised in a non-compet itive way by increased extracellular calcium concentrations. Spontaneous ac tivity in right atria was affected at concentrations > 10 muM beauvericin. The negative chronotropic effect was less pronounced than the negative inot ropic effect. In action potentials of electrically driven (1 Hz) papillary muscles, 10 muM beauvericin significantly decreased membrane resting potent ial until unexcitability of the preparation occurred. Despite depolarisatio n of the membrane the maximum rate of rise of the action potential was not changed. The action potential duration was shortened, but the decrease was only significant at times to 20% and 50% repolarisation. These data, derive d from the electrophysiological experiments, not only imply an effect on th e calcium current as suggested by the effects on contractility, but also an interaction with the sodium inward and potassium outward currents.