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Toxicon
2008 May 01;516:974-83. doi: 10.1016/j.toxicon.2008.01.004.
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Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels.
Cuypers E
,
Abdel-Mottaleb Y
,
Kopljar I
,
Rainier JD
,
Raes AL
,
Snyders DJ
,
Tytgat J
.
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In this study, we pharmacologically characterized gambierol, a marine polycyclic ether toxin which is produced by the dinoflagellate Gambierdiscus toxicus. Besides several other polycyclic ether toxins like ciguatoxins, this scarcely studied toxin is one of the compounds that may be responsible for ciguatera fish poisoning (CFP). Unfortunately, the biological target(s) that underlies CFP is still partly unknown. Today, ciguatoxins are described to specifically activate voltage-gated sodium channels by interacting with their receptor site 5. But some dispute about the role of gambierol in the CFP story shows up: some describe voltage-gated sodium channels as the target, while others pinpoint voltage-gated potassium channels as targets. Since gambierol was never tested on isolated ion channels before, it was subjected in this work to extensive screening on a panel of 17 ion channels: nine cloned voltage-gated ion channels (mammalian Na(v)1.1-Na(v)1.8 and insect Para) and eight cloned voltage-gated potassium channels (mammalian K(v)1.1-K(v)1.6, hERG and insect ShakerIR) expressed in Xenopus laevis oocytes using two-electrode voltage-clamp technique. All tested sodium channel subtypes are insensitive to gambierol concentrations up to 10 microM. In contrast, K(v)1.2 is the most sensitive voltage-gated potassium channel subtype with almost full block (>97%) and an half maximal inhibitory concentration (IC(50)) of 34.5 nM. To the best of our knowledge, this is the first study where the selectivity of gambierol is tested on isolated voltage-gated ion channels. Therefore, these results lead to a better understanding of gambierol and its possible role in CFP and they may also be useful in the development of more effective treatments.
Beekwilder,
Kv1.1 channels of dorsal root ganglion neurons are inhibited by n-butyl-p-aminobenzoate, a promising anesthetic for the treatment of chronic pain.
2003, Pubmed
Beekwilder,
Kv1.1 channels of dorsal root ganglion neurons are inhibited by n-butyl-p-aminobenzoate, a promising anesthetic for the treatment of chronic pain.
2003,
Pubmed
Benarroch,
Sodium channels and pain.
2007,
Pubmed
Bertaso,
Expression of voltage-gated K+ channels in human atrium.
2002,
Pubmed
Brendel,
Blockers of the Kv1.5 channel for the treatment of atrial arrhythmias.
2003,
Pubmed
Cameron,
The basis of the paradoxical disturbance of temperature perception in ciguatera poisoning.
1993,
Pubmed
Catterall,
International Union of Pharmacology. XXXIX. Compendium of voltage-gated ion channels: sodium channels.
2003,
Pubmed
Celesia,
Disorders of membrane channels or channelopathies.
2001,
Pubmed
Cuypers,
TRPV1 as a key determinant in ciguatera and neurotoxic shellfish poisoning.
2007,
Pubmed
,
Xenbase
Felipe,
Potassium channels: new targets in cancer therapy.
2006,
Pubmed
Ghiaroni,
Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells.
2005,
Pubmed
Ghiaroni,
Effect of ciguatoxin 3C on voltage-gated Na+ and K+ currents in mouse taste cells.
2006,
Pubmed
Harvey,
Dendrotoxins: structure-activity relationships and effects on potassium ion channels.
2004,
Pubmed
Hung,
Short report: persistent bradycardia caused by ciguatoxin poisoning after barracuda fish eggs ingestion in southern Taiwan.
2005,
Pubmed
Huys,
BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.
2004,
Pubmed
,
Xenbase
Inoue,
Inhibition of brevetoxin binding to the voltage-gated sodium channel by gambierol and gambieric acid-A.
2003,
Pubmed
Ito,
Pathological effects on mice by gambierol, possibly one of the ciguatera toxins.
2003,
Pubmed
Johnson,
The total synthesis of gambierol.
2005,
Pubmed
Johnson,
Total synthesis of gambierol: subunit coupling and completion.
2006,
Pubmed
Judge,
Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment.
2006,
Pubmed
Köhling,
Voltage-gated sodium channels in epilepsy.
2002,
Pubmed
LePage,
Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons.
2007,
Pubmed
Lewis,
Ciguatera: Australian perspectives on a global problem.
2006,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Louzao,
The sodium channel of human excitable cells is a target for gambierol.
2006,
Pubmed
Majumder,
Total synthesis of gambierol: the generation of the A-C and F-H subunits by using a C-glycoside centered strategy.
2006,
Pubmed
Nishiyama,
Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4.
2001,
Pubmed
Shieh,
Potassium channels: molecular defects, diseases, and therapeutic opportunities.
2000,
Pubmed
Sims,
A theoretical discourse on the pharmacology of toxic marine ingestions.
1987,
Pubmed
Srinivasan,
kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.
2002,
Pubmed
Stühmer,
Potassium channels expressed from rat brain cDNA have delayed rectifier properties.
1988,
Pubmed
,
Xenbase
Vicente,
Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+ channel in macrophages.
2006,
Pubmed
,
Xenbase
Wang,
Voltage-gated sodium channels as primary targets of diverse lipid-soluble neurotoxins.
2003,
Pubmed
Yasumoto,
The chemistry and biological function of natural marine toxins.
2001,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
Zlotkin,
The insect voltage-gated sodium channel as target of insecticides.
1999,
Pubmed
Zünkler,
Human ether-a-go-go-related (HERG) gene and ATP-sensitive potassium channels as targets for adverse drug effects.
2006,
Pubmed
