ToxSci Advance Access originally published online on February 2, 2005
Toxicological Sciences 2005 85(1):657-665; doi:10.1093/toxsci/kfi097
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Inhibition of Voltage-Gated Potassium Currents by Gambierol in Mouse Taste Cells
* Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, 41100 Modena, Italy; Graduate School of Life Sciences, Tohoku University, Sendai 981-8555, Japan; and Japan Food Research Laboratory, Tama Laboratories, Tokyo 206-0025, Japan
Received December 3, 2004; accepted January 27, 2004
Ciguatera is a food poisoning caused by toxins of Gambierdiscus toxicus, a marine dinoflagellate. The neurological features of this intoxication include sensory abnormalities, such as paraesthesia, heightened nociperception, and also taste alterations. Here, we have evaluated the effect of gambierol, one of the possible ciguatera toxins, on the voltage-gated ion currents in taste cells. Taste cells are excitable cells endowed with voltage-gated Na+, K+, and Cl– currents (INa, IK, and ICl, respectively). By applying the patch-clamp technique to single cells in isolated taste buds obtained from the mouse vallate papilla, we have recorded such currents and determined the effect of bath-applied gambierol. We found that this toxin markedly inhibited IK in the nanomolar range (IC50 of 1.8 nM), whereas it showed no significant effect on INa or ICl even at high concentration (1 µM). The block of IK was irreversible even after a 50-min wash. In addition to affecting the current amplitude, we found that gambierol significantly altered both the activation and inactivation processes of IK. In conclusion, unlike other toxins involved in ciguatera, such as ciguatoxins, which affect the functioning of voltage-gated sodium channels, the preferred molecular target of gambierol is the voltage-gated potassium channel, at least in taste cells. Voltage-gated potassium currents play an important role in the generation of the firing pattern during chemotransduction. Thus, gambierol may alter action potential discharge in taste cells and this could be associated with the taste alterations reported in the clinical literature.
Key Words: gambierol; ion currents; taste cell; patch clamp; ciguatera.
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