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Archives of Toxicology

, Volume 90, Issue 2, pp 479–488 | Cite as

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

  • Eva Alonso
  • Amparo Alfonso
  • Mercedes R. Vieytes
  • Luis M. BotanaEmail author
Biologics

Abstract

Although voltage-gated sodium channels (Na v ) 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 Na v channels. Currently, the availability of automated patch clamp platforms and also of stably transfected cell lines with human Na v 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 Na v 1.6 and 1.2 channels for PSP screening.

Keywords

Paralytic shellfish poisoning Automated patch clamp Sodium channels Saxitoxin 

Notes

Acknowledgments

The research leading to these results has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01 and Consellería de Cultura, Educación e OrdenaciónUniversitaria, GRC2013-016, and through AxenciaGalega de Innovación, Spain, ITC-20133020 SINTOX, IN852A 2013/16-3 MYTIGAL. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007–2013) under Grant Agreement Nos. 265409 µAQUA, 315285 CIGUATOOLS, and 312184 PHARMASEA.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Eva Alonso
    • 1
  • Amparo Alfonso
    • 1
  • Mercedes R. Vieytes
    • 2
  • Luis M. Botana
    • 1
    Email author
  1. 1.Departamento de Farmacología, Facultad de VeterinariaUniversidad de Santiago de CompostelaLugoSpain
  2. 2.Departamento de Fisiología, Facultad de VeterinariaUniversidad de Santiago de CompostelaLugoSpain

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