Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons

Autor: Jordi Molgó, Evelyne Benoit, César Mattei
Přispěvatelé: Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2014
Předmět:
Male
Potassium Channels
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Action Potentials
Nerve Fibers
Myelinated
Sodium Channels
Membrane Potentials
chemistry.chemical_compound
Mice
MESH: Sodium
MESH: Animals
MESH: Action Potentials
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Rana esculenta
MESH: Potassium Channels
Voltage-gated potassium channel
MESH: Nerve Fibers
Myelinated
Biochemistry
MESH: Rana esculenta
MESH: Axons
MESH: Cell Line
Tumor
MESH: Ions
Ciguatoxin
MESH: Rats
Sodium
Ionophore
chemistry.chemical_element
Lithium
MESH: Sodium Channels
Ciguatoxins
Cellular and Molecular Neuroscience
Valinomycin
Chlorides
Cell Line
Tumor
Ranvier's Nodes
MESH: Membrane Potentials
Animals
Channel blocker
MESH: Chlorides
MESH: Mice
Pharmacology
Ions
Tetraethylammonium
MESH: Lithium
Sodium channel
MESH: Ciguatoxins
MESH: Male
Axons
Rats
chemistry
MESH: Potassium
Biophysics
Potassium
MESH: Ranvier's Nodes
Zdroj: Neuropharmacology
Neuropharmacology, Elsevier, 2014, 85, pp.417-26. ⟨10.1016/j.neuropharm.2014.06.001⟩
ISSN: 1873-7064
0028-3908
DOI: 10.1016/j.neuropharm.2014.06.001⟩
Popis: International audience; Ciguatoxins, mainly produced by benthic dinoflagellate Gambierdiscus species, are responsible for a complex human poisoning known as ciguatera. Previous pharmacological studies revealed that these toxins activate voltage-gated Na+ channels. In frog nodes of Ranvier, ciguatoxins induce spontaneous and repetitive action potentials (APs) and increase axonal volume that may explain alterations of nerve functioning in intoxicated humans. The present study aimed determining the ionic mechanisms involved in Pacific ciguatoxin-1B (P-CTX-1B)-induced membrane hyperexcitability and subsequent volume increase in frog nodes of Ranvier, using electrophysiology and confocal microscopy. The results reveal that P-CTX-1B action is not dependent on external Cl- ions since it was not affected by substituting Cl- by methylsulfate ions. In contrast, substitution of external Na+ by Li+ ions suppressed spontaneous APs and prevented nodal swelling. This suggests that P-CTX-1B-modified Na+ channels are not selective to Li+ ions and/or are blocked by these ions, and that Na+ influx through Na+ channels opened during spontaneous APs is required for axonal swelling. The fact that the K+ channel blocker tetraethylammonium modified, but did not suppress, spontaneous APs and greatly reduced nodal swelling induced by P-CTX-1B indicates that K+ efflux might also be involved. This is supported by the fact that P-CTX-1B, when tested in the presence of both tetraethylammonium and the K+ ionophore valinomycin, produced the characteristic nodal swelling. It is concluded that, during the action of P-CTX-1B, water movements responsible for axonal swelling depend on both Na+ influx and K+ efflux. These results pave the way for further studies regarding ciguatera treatment.
Databáze: OpenAIRE
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