A delta-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles
| Autor: | Nicolas Gilles, Julien Barbier, Evelyne Benoit, Stefan H. Heinemann, Jordi Molgó, Philippe Favreau, Nitza Ilan, Hung Lamthanh, Dalia Gordon, André Ménez, Haijun Chen, Frédéric Le Gall |
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| Přispěvatelé: | Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Research Unit Molecular and Cellular Biophysics, Medical Faculty of the Friedrich Schiller University-Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Department of Plant Sciences, Tel Aviv University [Tel Aviv], Tel Aviv University (TAU) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
MESH: Sequence Homology
Amino Acid Xenopus MESH: Neurons Action Potentials Motor nerve Venom MESH: Amino Acid Sequence Biochemistry Sodium Channels MESH: Recombinant Proteins Cyprinodontiformes Mice 0302 clinical medicine MESH: Animals MESH: Xenopus Conotoxin Receptor Cells Cultured MESH: Action Potentials Neurons 0303 health sciences MESH: Muscle Skeletal biology Cardiac muscle Rana esculenta Anatomy Recombinant Proteins 3. Good health medicine.anatomical_structure MESH: Rana esculenta Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] MESH: Cells Cultured Amphibian MESH: Myocardium MESH: Rats Molecular Sequence Data Neuromuscular Junction In Vitro Techniques Neuromuscular junction MESH: Oocytes MESH: Sodium Channels 03 medical and health sciences MESH: Cyprinodontiformes biology.animal medicine Animals Humans Amino Acid Sequence Muscle Skeletal Molecular Biology MESH: Mice 030304 developmental biology MESH: Humans MESH: Molecular Sequence Data Sequence Homology Amino Acid Myocardium Cell Biology MESH: Conotoxins Rats Oocytes Biophysics Heterologous expression MESH: Neuromuscular Junction Conotoxins MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (6), pp.4680-4685. ⟨10.1074/jbc.M309576200⟩ Journal of Biological Chemistry, 2004, 279 (6), pp.4680-4685. ⟨10.1074/jbc.M309576200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M309576200⟩ |
| Popis: | We have isolated delta-conotoxin EVIA (delta-EVIA), a conopeptide in Conus ermineus venom that contains 32 amino acid residues and a six-cysteine/four-loop framework similar to that of previously described omega-, delta-, microO-, and kappa-conotoxins. However, it displays low sequence homology with the latter conotoxins. delta-EVIA inhibits Na+ channel inactivation with unique tissue specificity upon binding to receptor site 6 of neuronal Na+ channels. Using amphibian myelinated axons and spinal neurons, we showed that delta-EVIA increases the duration of action potentials by inhibiting Na+ channel inactivation. delta-EVIA considerably enhanced nerve terminal excitability and synaptic efficacy at the frog neuromuscular junction but did not affect directly elicited muscle action potentials. The neuronally selective property of delta-EVIA was confirmed by showing that a fluorescent derivative of delta-EVIA labeled motor nerve endings but not skeletal muscle fibers. In a heterologous expression system, delta-EVIA inhibited inactivation of rat neuronal Na+ channel subtypes (rNaV1.2a, rNaV1.3, and rNaV1.6) but did not affect rat skeletal (rNaV1.4) and human cardiac muscle (hNaV1.5) Na+ channel subtypes. delta-EVIA, in the range of concentrations used, is the first conotoxin found to affect neuronal Na+ channels without acting on Na+ channels of skeletal and cardiac muscle. Therefore, it is a unique tool for discriminating voltage-sensitive Na+ channel subtypes and for studying the distribution and modulation mechanisms of neuronal Na+ channels, and it may serve as a lead to design new drugs adapted to treat diseases characterized by defective nerve conduction. |
| Databáze: | OpenAIRE |
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