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Tetrodotoxin‐resistant voltage‐gated sodium channel Na v 1.8 constitutively interacts with ankyrin G
Author(s) -
Montersino Audrey,
Brachet Anna,
Ferracci Géraldine,
Fache MariePierre,
Angles d'Ortoli Stephanie,
Liu Wenjing,
RuedaBoroni Fanny,
Castets Francis,
Dargent Bénédicte
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12785
Subject(s) - ankyrin , sodium channel , tetrodotoxin , biology , nav1 , axon , ion channel , ankyrin repeat , microbiology and biotechnology , neuroscience , sodium , biophysics , chemistry , receptor , biochemistry , organic chemistry , gene
The tetrodotoxin‐resistant ( TTX ‐R) voltage‐gated sodium channel Na v 1.8 is predominantly expressed in peripheral afferent neurons, but in case of neuronal injury an ectopic and detrimental expression of Na v 1.8 occurs in neurons of the CNS . In CNS neurons, Na v 1.2 and Na v 1.6 channels accumulate at the axon initial segment, the site of the generation of the action potential, through a direct interaction with the scaffolding protein ankyrin G (ankG). This interaction is regulated by protein kinase CK 2 phosphorylation. In this study, we quantitatively analyzed the interaction between Na v 1.8 and ankG. GST pull‐down assay and surface plasmon resonance technology revealed that Na v 1.8 strongly and constitutively interacts with ankG, in comparison to what observed for Na v 1.2. An ion channel bearing the ankyrin‐binding motif of Na v 1.8 displaced the endogenous Na v 1 accumulation at the axon initial segment of hippocampal neurons. Finally, Na v 1.8 and ankG co‐localized in skin nerves fibers. Altogether, these results indicate that Na v 1.8 carries all the information required for its localization at ankG micro‐domains. The constitutive binding of Na v 1.8 with ankG could contribute to the pathological aspects of illnesses where Na v 1.8 is ectopically expressed in CNS neurons.The peripheral voltage‐gated sodium channel Na v 1.8 can be abnormally expressed in central nervous system (CNS) neurons in cases of neuronal injury. We here demonstrated that Na v 1.8 binds strongly and constitutively to the scaffolding protein ankyrin G. This indicates that Na v 1.8 concentrates at the ankyrin G micro‐domains and could disturb the electrophysiological signature of CNS neurons where it is ectopicaly expressed.