Florida red tides result in massive fish kills, and many human health problems, including neurotoxic shellfish poisoning. The organism responsible for red tides, Ptychodiscus brevis, produces extremely potent, lipophilic neurotoxins called brevetoxins. Brevetoxins exert their detrimental effects on the peripheral and central nervous systems as a result of binding to site 5 of the alpha subunit of voltage-gated sodium channels.
The aim of this proposal is to investigate the electrophysiological effects of brevetoxin on different subtypes of single voltage-gated sodium channels from the central nervous system. These studies will employ the technique of single cell voltage clamp on unitary sodium currents and will be performed on two cell lines derived from the rat central nervous system, which express different sodium channels subtypes. Chemically modified derivatives of brevetoxin, which have the potential for differential effects on different sodium channel subtypes, will be studied. At present, there are no such pharmacological tools known. These studies may lead to a better understanding of the neuronal effects of brevetoxin, and of the way brevetoxin causes neurotoxic shellfish poisoning.
