The sodium channel of human excitable cells is a target for gambierol.

Abstract

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.

CONCLUSION:

These results indicate that gambierol modulate ion fluxes by acting as a partial agonist of sodium channels.

• Authors: M Carmen Louzao, Eva Cagide, Mercedes R Vieytes, Makoto Sasaki, Haruhiko Fuwa, Takeshi Yasumoto, Luis M Botana
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 17 Issue 5-6 Pg. 257-68 ( 2006) ISSN: 1015-8987 [Print] Germany
• PMID: 16791001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ethers, Cyclic
• Polycyclic Compounds
• Sodium Channels
• Sodium-Calcium Exchanger
• gambierol
• Ciguatoxins
• ciguatoxin 2
• Saxitoxin
• neosaxitoxin
• Veratridine
• Calcium

Topics

• Calcium (metabolism)
• Cell Polarity (drug effects)
• Ciguatoxins (pharmacology)
• Ethers, Cyclic (pharmacology)
• Humans
• Membrane Potentials (drug effects)
• Neuroblastoma (drug therapy, metabolism)
• Neurons (drug effects, metabolism)
• Polycyclic Compounds (pharmacology)
• Saxitoxin (analogs & derivatives, pharmacology)
• Sodium Channels (drug effects, metabolism)
• Sodium-Calcium Exchanger (antagonists & inhibitors, drug effects, metabolism)
• Tumor Cells, Cultured
• Veratridine (pharmacology)