Sea anemones neurotoxins as tools to study the physiology of voltage-gated potassium channels

• Grant number: 09/07128-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2010
• End date: December 31, 2012
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Jose Eduardo Pereira Wilken Bicudo
• Grantee: Diego Jose Orts y Belato
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 11/21031-6 - Analysis of the mechanism of action involved in the selective activity of Abe III 1.3 in voltage-dependent K+ channels, BE.EP.MS

Abstract

The sea anemones venom is a rich source of bioactive compounds, including peptide toxins which are tools for studying the structure and function of voltage-dependent channels K+ (KV). In this work, four neurotoxins were purified from the venom of the sea anemones Actinia bermudenesis and Bunodosoma caissarum. AbeTx1 and BcsTx4 have a structural motif similar to that of kappa-toxins and functional and structural analysis showed that they are the first members of a new type (type 5) of sea anemone neurotoxins acting on KV channels. Moreover, the structural analysis of BcsTx1 and BcsTx2 toxins allowed us to conclude that they are members of the previously described type 1 (subtype 1b) of sea anemone neurotoxins. Functional characterization was performed by means of a wide electrophysiological screening on different KV channels using oocytes of Xenopus laevis and electrophysiological measurements were performed employing the voltage-clamp technique. AbeTx1, BcsTx1 and BcsTx2 (3 M) showed a selective activity for KV1.1-KV1.3, KV1.6 and Shaker IR, while BcsTx4 (3 µM) only blocks KV1.1, KV1.2 and KV1.6. The mechanisms involved in potency and selectivity were discussed based on the results obtained and physiological analyses have provided new insights on the role of these toxins in the physiology of the sea anemones.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ORTS, DIEGO J. B.; PEIGNEUR, STEVE; SILVA-GONCALVES, LAIZ COSTA; ARCISIO-MIRANDA, MANOEL; BICUDO, JOSE EDUARDO P. W.; TYTGAT, JAN. AbeTx1 Is a Novel Sea Anemone Toxin with a Dual Mechanism of Action on Shaker-Type K+ Channels Activation. MARINE DRUGS, v. 16, n. 10, OCT 2018. (16/13368-4, 16/17951-6, 09/07128-7, 11/21031-6)

PEIGNEUR, STEVE; ORTS, DIEGO J. B.; PRIETO DA SILVA, ALVARO R.; OGUIURA, NANCY; BONI-MITAKE, MALVINA; DE OLIVEIRA, EDUARDO B.; ZAHARENKO, ANDRE J.; DE FREITAS, JOSE C.; TYTGAT, JAN. Crotamine Pharmacology Revisited: Novel Insights Based on the Inhibition of K-V Channels. MOLECULAR PHARMACOLOGY, v. 82, n. 1, p. 90-96, JUL 2012. (09/07128-7)

ORTS, DIEGO J. B.; PEIGNEUR, STEVE; MADIO, BRUNO; CASSOLI, JULIANA S.; MONTANDON, GABRIELA G.; PIMENTA, ADRIANO M. C.; BICUDO, JOSE E. P. W.; FREITAS, JOSE C.; ZAHARENKO, ANDRE J.; TYTGAT, JAN. Biochemical and Electrophysiological Characterization of Two Sea Anemone Type 1 Potassium Toxins from a Geographically Distant Population of Bunodosoma caissarum. MARINE DRUGS, v. 11, n. 3, p. 655-679, MAR 2013. (11/21031-6, 09/07128-7)

ORTS, DIEGO J. B.; MORAN, YEHU; COLOGNA, CAMILA T.; PEIGNEUR, STEVE; MADIO, BRUNO; PRAHER, DANIELA; QUINTON, LOIC; DE PAUW, EDWIN; BICUDO, JOSE E. P. W.; TYTGAT, JAN; et al. BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker. FEBS Journal, v. 280, n. 19, p. 4839-4852, OCT 2013. (11/21031-6, 09/07128-7)