Evaluation of toxicity equivalent factors of paralytic shellfish poisoning toxins in seven human sodium channels types by an automated high throughput electrophysiology system.

Alonso E , Alfonso A, Vieytes MR, Botana LM.
Arch Toxicol. 2015 Jan 9.

Abstract

Although voltage-gated sodium channels (NaV) are the cellular target of paralytic shellfish poisoning (PSP) toxins and that patch clamp electrophysiology is the most effective way of studying direct interaction of molecules with these channels, nowadays, this technique is still reduced to more specific analysis due to the difficulties of transforming it in a reliable throughput system. Actual functional methods for PSP detection are based in binding assays using receptors but not functional Nav channels. Currently, the availability of automated patch clamp platforms and also of stably transfected cell lines with human Nav channels allow us to introduce this specific and selective method for fast screenings in marine toxin detection. Taking advantage of the accessibility to pure PSP standards, we calculated the toxicity equivalent factors (TEFs) for nine PSP analogs obtaining reliable TEFs in human targets to fulfill the deficiencies of the official analytic methods and to verify automated patch clamp technology as a fast and reliable screening method for marine toxins that interact with the sodium channel. The main observation of this work was the large variation of TEFs depending on the channel subtype selected, being remarkable the variation of potency in the 1.7 channel subtype and the suitability of Nav 1.6 and 1.2 channels for PSP screening.

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