788
Chem. Res. Toxicol. 2006, 19, 788-793
Changes in Membrane Potential: An Early Signal Triggered by Neurologically Active Phycotoxins M. C. Louzao,† M. R. Vieytes,‡ T. Yasumoto,§ M. Yotsu-Yamashita,| and L. M. Botana*,† Departamento de Farmacologia, Facultad de Veterinaria de Lugo, and Departamento de Fisiologia Animal, Facultad de Veterinaria, UniVersidad de Santiago de Compostela, 27002 Lugo, Spain, Tama Laboratory, Japan Food Research Laboratories, Tokyo 206-0025, Japan, and Laboratory of Food and Biodynamic Chemistry, DiVision of Bioscience and Biotechnology for Future Bioindustry, Graduate School of Agricultural Science, Tohoku UniVersity, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan ReceiVed NoVember 14, 2005
Most common phycotoxin poisoning syndromes have important neurological symptoms. However, little is known of the cellular and molecular targets of many of the phycotoxins that produce those human intoxications. We explore the effect of representative toxins on the membrane potential in human neuroblastoma cells by using a fluorimetric assay. Results presented in this study demonstrate that maitotoxin, palytoxins, brevetoxins, and ciguatoxins triggered a dose-dependent membrane depolarization. Mechanisms responsible for the toxins-induced changes in membrane potential are always related to a direct action of the compounds on membrane ion fluxes. This initial screening of the phycotoxins effect is the starting point to lately develop functional methods of detection. Introduction Ingestion of seafood contaminated with algal toxins results in seafood poisoning syndromes: paralytic shellfish poisoning, neurotoxic shellfish poisoning, diarrhetic shellfish poisoning, ciguatera fish poisoning, and palytoxin (PLTX)1 poisoning (1). Saxitoxin (STX) is the representative component of the paralytic shellfish poisoning group (2-4). Paralytic shellfish poisoning toxins bind with high affinity to site 1 on the voltage-dependent sodium channel, inhibiting channel conductance and thereby causing blockade of neuronal activity (5, 6). Most countries have monitoring programs for mollusk toxicity (particularly paralytic shellfish poisoning). These monitoring studies involve intensive analysis of a large number of shellfish samples, where the regulatory limit threshold is 80 µg STX equivalent/100 g of mollusk meat (7, 8). Paralytic shellfish poisoning toxins were measurable at
