1. Batrachotoxinin-A N-methylanthranilate, a new fluorescent ligand for voltage-sensitive sodium channels.
- Author
-
Brown GB and Bradley RJ
- Subjects
- Animals, Batrachotoxins chemical synthesis, Binding, Competitive, Cerebral Cortex metabolism, Fluorescent Dyes chemical synthesis, Ligands, Mice, Microscopy, Fluorescence, Batrachotoxins metabolism, Ion Channels metabolism, Peripheral Nerves metabolism
- Abstract
Batrachotoxin and its derivatives have become important tools for the study of membrane excitability by virtue of their effects on voltage-sensitive sodium channels. Recent studies have shown that the 2,4-dimethylpyrrole carboxylate ester normally occurring in the 20-alpha position of batrachotoxin may be replaced by a benzoate moiety without loss of activity. We have now extended this series of active batrachotoxin derivatives and report here the synthesis of batrachotoxinin-A 20-alpha-N-methylanthranilate. The new fluorescent compound is highly toxic (LD50 approx. 15 micrograms/kg, i.p. mouse) and binds to the same receptor site of voltage-sensitive sodium channels as batrachotoxin with an equilibrium dissociation constant Kd = 180 nM (in the presence of scorpion toxin). These fluorescence and binding properties have been exploited to achieve successful visualization of sodium channels at mammalian nodes of Ranvier. Batrachotoxinin-A 20-alpha-N-methylanthranilate should prove to be a useful compound for studies of sodium channel distribution and for investigations of the microenvironment of the batrachotoxin binding site.
- Published
- 1985
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