A Comparative Study of the Effect of Ciguatoxins on Voltage-Dependent Na+ and K+ Channels in Cerebellar Neurons

A Comparative Study of the Effect of Ciguatoxins on Voltage-Dependent Na+ and K+ Channels in Cerebellar Neurons

Sheila Pérez,Carmen Vale,Eva Alonso,Carmen Alfonso,Paula Rodríguez,Paz Otero,Amparo Alfonso,Paulo Vale,Masahiro Hirama,Mercedes R. Vieytes,Luis M. Botana;Sheila Pérez;Carmen Vale;Eva Alonso;Carmen Alfonso;Paula Rodríguez;Paz Otero;Amparo Alfonso;Paulo Vale;Masahiro Hirama;Mercedes R. Vieytes;Luis M. Botana;
Chemical research in toxicology 2011 Vol. 24 pp. 587-596
184
botana2011chemicala

Abstract

Ciguatera is a global disease caused by the consumption of certain warm-water fish (ciguateric fish) that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. The effect of ciguatoxin standards and contaminated ciguatoxin samples was evaluated by electrophysiological recordings in cultured cerebellar neurons. The toxins affected both voltage-gated sodium (Nav) and potassium channels (Kv) although with different potencies. CTX 3C was the most active toxin blocking the peak inward sodium currents, followed by P-CTX 1B and 51-OH CTX 3C. In contrast, P-CTX 1B was more effective in blocking potassium currents. The analysis of six different samples of contaminated fish, in which a ciguatoxin analogue of mass 1040.6, not identical with the standard 51-OH CTX 3C, was the most prevalent compound, indicated an additive effect of the different ciguatoxins present in the samples. The results presented here constitute the first comparison of the potencies of three different purified ciguatoxins on sodium and potassium channels in the same neuronal preparation and indicate that electrophysiological recordings from cultured cerebellar neurons may provide a valuable tool to detect and quantify ciguatoxins in the very low nanomolar range.

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