Abstract
Four neurotoxins that activate the action potential Na+ ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin is a noncompetitive inhibitor of activation by each of these toxins (KI = 4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ ionophore: two regulatroy components, which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin.
MeSH Terms
Aconitine/pharmacology
Action Potentials/drug effects
Alkaloids/pharmacology
Animals
Batrachotoxins/pharmacology
Biological Transport
Cell Line
Cell Membrane/drug effects,metabolism
Clone Cells
Kinetics
Neuroblastoma
Peptides/pharmacology
Scorpions
Sodium/metabolism
Structure-Activity Relationship
Tetrodotoxin/pharmacology
Toxins, Biological/pharmacology
Venoms/pharmacology
Veratridine/pharmacology
Chemicals
Alkaloids
Batrachotoxins
Peptides
Toxins, Biological
Venoms
Tetrodotoxin
Veratridine
Sodium
Aconitine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Catterall W A
References (22)
22 references, click to expand
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