The sodium channel of human excitable cells is a target for gambierol.
BACKGROUND
Gambierol is a polycyclic ether toxin with the same biogenetic origin as ciguatoxins. Gambierol has been associated with neurological symptoms in humans even though its mechanism of action has not been fully characterized.


METHODS
We studied the effect of gambierol in human neuroblastoma cells by using bis-oxonol to measure membrane potential and FURA-2 to monitor intracellular calcium.


RESULTS
We found that this toxin: i) produced a membrane depolarization, ii) potentiated the effect of veratridine on membrane potential iii) decreased ciguatoxin-induced depolarization and iv) increased cytosolic calcium in neuroblastoma cells.


CONCLUSIONS
These results indicate that gambierol modulate ion fluxes by acting as a partial agonist of sodium channels.
Louzao
M Carmen
MC
Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
Cagide
Eva
E
Vieytes
Mercedes R
MR
Sasaki
Makoto
M
Fuwa
Haruhiko
H
Yasumoto
Takeshi
T
Botana
Luis M
LM
D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002922:Ciguatoxins / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012530:Saxitoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014701:Veratridine / Q000494:pharmacology; D035964:Oxocins
D002118:Calcium; D002922:Ciguatoxins; D004988:Ethers, Cyclic; D011083:Polycyclic Compounds; D012530:Saxitoxin; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D014701:Veratridine; C435770:gambierol; D035964:Oxocins; C082191:ciguatoxin 2; C034902:neosaxitoxin