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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January 2014
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December 10 2013
Nedd4-2 (NEDD4L) controls intracellular Na+-mediated activity of voltage-gated sodium channels in primary cortical neurons
Jenny A. Ekberg;
Jenny A. Ekberg
1
*School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4001, Australia
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Natasha A. Boase;
Natasha A. Boase
1
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
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Grigori Rychkov;
Grigori Rychkov
1
‡School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Jantina Manning;
Jantina Manning
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
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Philip Poronnik;
Philip Poronnik
§School of Medical Sciences & Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
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Sharad Kumar
Sharad Kumar
2
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
∥Department of Medicine, University of Adelaide, Adelaide, SA 5005, Australia
¶Division of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia
2To whom correspondence should be addressed (email sharad.kumar@health.sa.gov.au).
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Biochem J (2014) 457 (1): 27–31.
Article history
Received:
September 25 2013
Revision Received:
October 22 2013
Accepted:
October 24 2013
Accepted Manuscript online:
October 24 2013
Citation
Jenny A. Ekberg, Natasha A. Boase, Grigori Rychkov, Jantina Manning, Philip Poronnik, Sharad Kumar; Nedd4-2 (NEDD4L) controls intracellular Na+-mediated activity of voltage-gated sodium channels in primary cortical neurons. Biochem J 1 January 2014; 457 (1): 27–31. doi: https://doi.org/10.1042/BJ20131275
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