Tetrodotoxin (TTX) is a highly specific blocker of voltage-gated sodium channels. The dissociation constant of block varies with different channel isoforms. Until recently, channel resistance was thought to be primarily imparted by amino acid substitutions at a single position in domain I. Recent work reveals a novel site for tetrodotoxin resistance in the P-region of domain IV.

The action of neurotoxins on tetrodotoxin-insensitive sodium channels in cultured rat muscle cells has been studied by ion flux methods. The alkaloid neurotoxins batrachotoxin, veratridine, and aconitine act at a common receptor site to cause persistent activation of sodium channels. Batrachotoxin is a full agonist, while veratridine and aconitine are partial agonists activating 8% and 1% of so...

Veratridine, an activator of action potential Na(+) ionophores, stimulated passive Na(+) uptake by electrically excitable neuroblastoma and muscle cells but had no effect on clonal cell lines defective in Na(+)-ionophore activity. Veratridine-dependent Na(+) uptake was completely inhibited by tetrodotoxin, a specific inhibitor of the action potential Na(+) ionophore. Half-maximal inhibition was...