Nedd4-2(NEDD4L) controls intracellular Na(+)-mediated activity of voltage-gated sodium channels in primary cortical neurons.

Ekberg, Jenny A, Boase, Natasha A, Rychkov, Grigori, Manning, Jantina, Poronnik, Philp, & Kumar, Sharad (2014) Nedd4-2(NEDD4L) controls intracellular Na(+)-mediated activity of voltage-gated sodium channels in primary cortical neurons. Biochemical Journal, 457(1), pp. 27-31.

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Abstract

Nedd4-2, a HECT (homologous with E6-associated protein C-terminus)-type ubiquitin protein ligase, has been implicated in regulating several ion channels, including Navs (voltage-gated sodium channels). In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions under which Nedd4-2 mediates native Nav regulation remain uncharacterized. Using Nedd4-2-deficient mice, we demonstrate in the present study that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na(+), but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav activities. The results of the present study provide the first physiological evidence for an essential function of Nedd4-2 in regulating Navs in the central nervous system.

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ID Code: 68270
Item Type: Journal Article
Refereed: Yes
Keywords: neuron, patch-clamp technique, sodium transport,
DOI: 10.1042/BJ20131275
ISSN: 0264-6021
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900) > Neurosciences not elsewhere classified (110999)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 11 Mar 2014 05:52
Last Modified: 19 Mar 2014 04:53

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