Ekberg, J.Boase, N.Rychkov, G.Manning, J.Poronnik, P.Kumar, S.2015-03-122015-03-122014Biochemical Journal, 2014; 457(1):27-310264-60211470-8728http://hdl.handle.net/2440/89731Nedd4-2, 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.en© The Authors Journal compilation © 2014 Biochemical Societyneuron; patch-clamp technique; sodium transport; ubiquitin protein ligaseNedd4-2 (NEDD4L) controls intracellular Na⁺ -mediated activity of voltage-gated sodium channels in primary cortical neuronsNedd4-2 (NEDD4L) controls intracellular Na(+) -mediated activity of voltage-gated sodium channels in primary cortical neuronsJournal article002013425810.1042/BJ201312750003337179000032-s2.0-8489008165716672Rychkov, G. [0000-0002-2788-2977]Manning, J. [0000-0001-9142-6135]Kumar, S. [0000-0001-7126-9814]