The effect of the Fusarium metabolite beauvericin on electromechanical and -physiological properties in isolated smooth and heart muscle preparations of guinea pigs.
The electromechanical and -physiological effects of beauvericin were studied in isolated smooth and heart muscle preparations of the guinea pig. Beauvericin concentration-dependently decreased the force of contraction in precontracted (60 mM KCl) terminal ilea with an IC50 of 0.86 microM, and in electrically stimulated (1 Hz) papillary muscles with an IC50 of 18 microM. This negative inotropic effect in papillary muscles was antagonised in a non-competitive way by increased extracellular calcium concentrations. Spontaneous activity in right atria was affected at concentrations > 10 microM beauvericin. The negative chronotropic effect was less pronounced than the negative inotropic effect. In action potentials of electrically driven (1 Hz) papillary muscles, 10 microM beauvericin significantly decreased membrane resting potential until unexcitability of the preparation occurred. Despite depolarisation 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, derived from the electrophysiological experiments, not only imply an effect on the calcium current as suggested by the effects on contractility, but also an interaction with the sodium inward and potassium outward currents.
Institute of Pharmacology and Toxicology, University of Vienna, Althansstr. 14, A-1090 Vienna, Austria. rosa.lemmens@univie.ac.at
R
R
Lemmens-Gruber
B
B
Rachoy
E
E
Steininger
K
K
Kouri
P
P
Saleh
R
R
Krska
R
R
Josephs
M
M
Lemmens
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D003864:Depression, Chemical; D047630:Depsipeptides; D005260:Female; D005670:Fusarium / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D007082:Ileum; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects*; D010455:Peptides
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D010455:Peptides; C004456:beauvericin; D002118:Calcium