Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

Cyril Goudet; Tania Ferrer; Loipa Galàn; Adriana Artiles; Cesar F V Batista; Lourival D Possani; Julio Alvarez; Abel Aneiros; Jan Tytgat

doi:10.1038/sj.bjp.0704361

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Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

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Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

Cyril Goudet, Tania Ferrer, Loipa Galàn, Adriana Artiles, Cesar F V Batista, Lourival D Possani, Julio Alvarez, Abel Aneiros et Jan Tytgat

British journal of pharmacology, Vol.134(6), pp.1195-1206

11/2001

DOI: https://doi.org/10.1038/sj.bjp.0704361

PMID: 11704639

Résumé

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Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 μM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels.

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Titre: Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels
Créateurs - sans rôle: Cyril Goudet - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Tania Ferrer - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Loipa Galàn - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Adriana Artiles - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Cesar F V Batista - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Lourival D Possani - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Julio Alvarez - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Abel Aneiros - Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium Instituto de Cardologia y Cirugia Cardiovascular, Apartado de Correos 6152, 10600 La Habana, Cuba Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, Mexico Instituto de Oceanologia, Loma y 37 Alturas del Vedado, 10600 La Habana, Cuba
Jan Tytgat - KU Leuven
Détails de publication: British journal of pharmacology, Vol.134(6), pp.1195-1206
Nombre de pages: 12
Identifiants: 99139470809311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English
Type de ressource: Journal article