Batrachotoxinin-A N-methylanthranilate, a new fluorescent ligand for voltage-sensitive sodium channels.
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.
Brown
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GB
Bradley
R J
RJ
D000818:Animals; D001496:Batrachotoxins / Q000138:chemical synthesis / Q000378:metabolism*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis; D007473:Ion Channels / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008856:Microscopy, Fluorescence; D010525:Peripheral Nerves / Q000378:metabolism*
D001496:Batrachotoxins; D005456:Fluorescent Dyes; D007473:Ion Channels; D008024:Ligands; C045684:batrachotoxinin-A N-methylanthranilate