Some actions of purified toxins from Bungarus fasciatus venom on isolated pig-heart mitochondria.
I. In the presence of succinate as an oxidation substrate, neurotoxins alpha, beta and gamma induce the following. Firstly, an increasing stimulation of oxygen uptake, which in potentiated by 25 muM Ca2+, Mg2+ 1.3 mM completely inhibits the effect of toxin alpha but not of toxins beta and gamma. Secondly, a depletion of the Mg2+, Ca2+ and K+ content of the water-soluble and membrane-bound mitochondrial compartments, following complex kinetics, which suggest a multistep interaction mechanism of the toxins with the mitochondria. 25 muM Ca2+ also potentiates the effect of the toxins on these ionic flows. Thirdly, no decrease of turbidity with toxin alpha, and a limited decrease with toxins beta and gamma. 2. In the absence of respiration, the neurotoxins induce a cationic depletion, the kinetics of which are different than with succinate, suggesting an instantaneous maximal effect on the inner membrane. Toxins beta and gamma (but not alpha) induce, under these conditions, a turbidity decrease of large amplitude, which is proportional to the amount of toxin added and tends to reach a maximum. With gamma toxin this turbidity decrease is faster than the rate of water uptake (which never exceeds 18%) indicating that it is due rather to structural modifications than to swelling. The same is observed with beta toxin, provided the mitochondrial protein concentration to be lower than 0.7 mg/ml. For higher concentrations, a continuous decrease of turbidity with a considerable uptake of water probably reflects the onset of phospholipasic activities. 3. It is postulated that structural modifications of the mitochondrial membranes are initiated which lead to the loss of their selective impermeability. The simultaneous loss of respiratory control with succinate may be due to the direct (though Ca2+-potentiated) displacement of the fraction of the membrane-bound Mg2+ ions which controls its energy-transducing properties. 4. In addition, correlations between the effects of the toxins on mitochondria and their neurotoxicity in vivo are discussed.
D000818:Animals; D001693:Biological Transport, Active; D002038:Bungarotoxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D013552:Swine
D002038:Bungarotoxins; D008274:Magnesium; D011188:Potassium; D002118:Calcium