Molecular mechanism of cardiotoxin action on axonal membranes.
Cardiotoxin isolated from Naja mossambica mossambica selectively deactivates the sodium-potassium activated adenosine triphosphatase of axonal membranes. Tetrodotoxin binding and acetylcholinesterase activities are unaffected by cardiotoxin treatment. The details of association of cardiotoxin with the axonal membrane were studied by following the deactivation of the sodium-potassium activated adenosine triphosphatase and by direct binding measurements with a tritiated derivative of the native cardiotoxin. The maximal binding capacity of the membrane is 42-50 nmol of cardiotoxin/mg of membrane protein. The high amount of binding suggests association of the toxin with the lipid phase of the membrane. It has been shown that cardiotoxin first associates rapidly and reversibly to membrane lipids, then, in a second step, it induces a rearrangement of the membrane structure which produces and irreversible deactivation of the sodium-potassium activated adenosine triphosphatase. Solubilization of the membrane-bound ATPase with Lubrol WX gives an active enzyme species that is resistant to cardiotoxin-induced deactivation. Cardiotoxin binding to the membrane is prevented by high concentrations of Ca 2+ and dibucaine. Although cardiotoxins and neurotoxins of cobra venom have large sequence homologies, their mode of action on membranes is very different. The cardiotoxin seems to bind to the lipid phase of the axonal membrane and inhibits the sodium-potassium activated adenosine triphosphatase, whereas the neurotoxin associates with a protein receptor in the post-synaptic membrane and blocks acetylcholine transmission.
D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D001369:Axons / Q000187:drug effects*; D003386:Brachyura; D002118:Calcium / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008566:Membranes / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011485:Protein Binding; D012910:Snake Venoms / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D003902:Detergents; D010455:Peptides; D012910:Snake Venoms; D014701:Veratridine; D012964:Sodium; D009597:4-Nitrophenylphosphatase; D000251:Adenosine Triphosphatases; D003992:Dibucaine; D011188:Potassium; D002118:Calcium