Blockade of nicotinic currents in hippocampal neurons defines methyllycaconitine as a potent and specific receptor antagonist.
Methyllycaconitine, a toxin isolated from the seeds of Delphinium brownii, inhibited acetylcholine- and anatoxin-induced whole-cell currents in cultured fetal rat hippocampal neurons, at picomolar concentrations. This antagonism was specific, concentration dependent, reversible, and voltage independent. Furthermore, methyllycaconitine inhibited 125I-alpha-bungarotoxin binding to adult rat hippocampal membranes, protected against the alpha-bungarotoxin-induced pseudoirreversible blockade of nicotinic currents, and shifted the concentration-response curve of acetylcholine to the right in fetal rat hippocampal neurons, suggesting a possible competitive mode of action for this toxin. Remarkably low concentrations of methyllycaconitine (1-1000 fM) decreased the frequency of anatoxin-induced single-channel openings, with no detectable decrease in the mean channel open time. These actions of methyllycaconitine commend this neurotoxin for the characterization of the alpha-bungarotoxin-sensitive subclass of neuronal nicotinic receptors, which has hitherto eluded functional demonstration.
Alkondon
M
M
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Pereira
E F
EF
Wonnacott
S
S
Albuquerque
E X
EX
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D000087522:Cyanobacteria Toxins; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008387:Marine Toxins / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D052998:Microcystins; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018733:Nicotinic Antagonists; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014118:Toxins, Biological
D001427:Bacterial Toxins; D002038:Bungarotoxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D018733:Nicotinic Antagonists; D014118:Toxins, Biological; C054634:methyllycaconitine; D000157:Aconitine