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Type: Journal article
Title: Nedd4-2 (NEDD4L) controls intracellular Na⁺ -mediated activity of voltage-gated sodium channels in primary cortical neurons
Other Titles: Nedd4-2 (NEDD4L) controls intracellular Na(+) -mediated activity of voltage-gated sodium channels in primary cortical neurons
Author: Ekberg, J.
Boase, N.
Rychkov, G.
Manning, J.
Poronnik, P.
Kumar, S.
Citation: Biochemical Journal, 2014; 457(1):27-31
Publisher: Portland Press
Issue Date: 2014
ISSN: 0264-6021
Statement of
Jenny A. Ekberg, Natasha A. Boase, Grigori Rychkov, Jantina Manning, Philip Poronnik and Sharad Kumar
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.
Keywords: neuron; patch-clamp technique; sodium transport; ubiquitin protein ligase
Rights: © The Authors Journal compilation © 2014 Biochemical Society
DOI: 10.1042/BJ20131275
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