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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity
Journal of Neurochemistry, Volume 107, No. 4, Year 2008
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Description
Gymnodimines (GYMs) are phycotoxins exhibiting unusual structural features including a spirocyclic imine ring system and a trisubstituted tetrahydrofuran embedded within a 16-membered macrocycle. The toxic potential and the mechanism of action of GYM-A, highly purified from contaminated clams, have been assessed. GYM-A in isolated mouse phrenic hemidiaphragm preparations produced a concentration- and time-dependent block of twitch responses evoked by nerve stimulation, without affecting directly elicited muscle twitches, suggesting that it may block the muscle nicotinic acetylcholine (ACh) receptor (nAChR). This was confirmed by the blockade of miniature endplate potentials and the recording of subthreshold endplate potentials in GYM-A paralyzed frog and mouse isolated neuromuscular preparations. Patch-clamp recordings in Xenopus skeletal myocytes revealed that nicotinic currents evoked by constant iontophoretical ACh pulses were blocked by GYM-A in a reversible manner. GYM-A also blocked, in a voltage-independent manner, homomeric human α7 nAChR expressed in Xenopus oocytes. Competition-binding assays confirmed that GYM-A is a powerful ligand interacting with muscle-type nAChR, heteropentameric α3β2, α4β2, and chimeric α7-5HT3 neuronal nAChRs. Our data show for the first time that GYM-A broadly targets nAChRs with high affinity explaining the basis of its neurotoxicity, and also pave the way for designing specific tests for accurate GYM-A detection in shellfish samples. © 2008 The Authors.
Authors & Co-Authors
Kharrat, Riadh
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Tunisia, Tunis
Institut Pasteur de Tunis
Servent, Denis
France, Gif-sur-yvette
Institut de Biologie et de Technologies de Saclay
Girard, Emmanuelle
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Ouanounou, Gilles
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Amar, Muriel
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Marrouchi, Riadh
Tunisia, Tunis
Institut Pasteur de Tunis
Benoit, Evelyne
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Molgó, Jordi J.
France, Gif-sur-yvette
Laboratoire Neurobiologie Cellulaire et Moléculaire Cnrs Upr 9040
Statistics
Citations: 117
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1111/j.1471-4159.2008.05677.x
ISSN:
00223042
e-ISSN:
14714159
Research Areas
Environmental