Ciguatoxin extracted from poisonous moray eels Gymnothorax javanicus triggers acetylcholine release from Torpedo cholinergic synaptosomes via reversed Na(+)-Ca2+ exchange.
Ciguatoxin (CTX) (0.1 pM to 10 nM) added to a suspension of Torpedo synaptosomes incubated in Ca(2+)-free medium caused no detectable acetylcholine (ACh) release. However, subsequent addition of Ca2+ caused a large ACh release that depended on time of exposure, dose of CTX and on [Ca2+]. Tetrodotoxin completely prevented CTX-induced Ca(2+)-dependent ACh release. Simultaneous blockade of Ca2+ channel subtypes by FTX, a toxin extracted from the venom of the spider Agelenopsis aperta, omega-conotoxin and Gd3+ did not prevent ACh release caused by CTX, upon addition of Ca2+. These results suggest that CTX activates the reversed operation of the Na+/Ca2+ exchange system allowing the entry of Ca2+ in exchange for Na+. It is concluded that Torpedo synaptosomes are endowed with Na+ channels sensitive to pico- to nanomolar concentrations of CTX.
Molgó
J
J
Département de Neuropharmacologie, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Gaudry-Talarmain
Y M
YM
Legrand
A M
AM
Moulian
N
N
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002922:Ciguatoxins / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004524:Eels / Q000378:metabolism*; D066298:In Vitro Techniques; D007474:Ion Exchange; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014101:Torpedo / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002922:Ciguatoxins; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine