ALLOSTERIC MODULATION OF NEUROTOXIN BINDING TO VOLTAGE-SENSITIVE SODIUM-CHANNELS BY PTYCHODISCUS-BREVIS TOXIN-2

  • 1 March 1987
    • journal article
    • research article
    • Vol. 31  (3) , 273-278
Abstract
The effects of Ptychodiscus brevis toxin 2 (PbTx-2) on the binding of neurotoxins at four different neurotoxin receptor sites on voltage-sensitive sodium channels in rat brain synaptosomes were examined. Binding of saxitoxin at neurotoxin receptor site 1 and Leiurus quinquestriatus .alpha.-scorpion toxin (LqTx) at neurotoxin receptor site 3 was unaffected. PbTx-2 enhanced binding of batrachotoxinin A 20-.alpha.-benzoate (BTX-B) to neurotoxin receptor site 2 and Centruroides suffusus suffusus .beta.-scorpion toxin (CsTx II) to site 4 on sodium channels. These results support the proposal that PbTx-2 and related toxins act at a new receptor site (site 5) that has not been previously analyzed in binding experiments. Half-maximal effects of PbTx-2 were observed in the range of 20-50 nM PbTx-2. The enhancmeent of BTX-B binding was reduced by depolarization. Saturating concentrations of PbTx-2 reduced Kd values for binding of BTX-B and CsTx-II 2.9-fold and 2.6 fold, respectively. The effects of PbTx-2 and LqTx in enhancing BTX-B binding were synergistic. A model involving both preferential binding of BTX-B, PbTx-2, LqTx, and CsTx II to active states of sodium channels and allosteric interactions among the four receptor sites at which these toxins act accommodates these and previous results.

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