title: SGK3 Sensitivity of Voltage Gated K+ Channel Kv1.5 (KCNA5).
abstract: BACKGROUND
  The serum &amp; glucocorticoid inducible kinase isoform SGK3 is a powerful regulator of several transporters, ion channels and the Na+/K+ ATPase. Targets of SGK3 include the ubiquitin ligase Nedd4-2, which is in turn a known regulator of the voltage gated K+ channel Kv1.5 (KCNA5). The present study thus explored whether SGK3 modifies the activity of the voltage gated K+ channel KCNA5, which participates in the regulation of diverse functions including atrial cardiac action potential, activity of vascular smooth muscle cells, insulin release and tumour cell proliferation.
  
  
  METHODS
  cRNA encoding KCNA5 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild-type SGK3, constitutively active S419DSGK3, inactive K191NSGK3 and/or wild type Nedd4-2. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp.
  
  
  RESULTS
  Voltage gated current in KCNA5 expressing Xenopus oocytes was significantly enhanced by wild-type SGK3 and S419DSGK3, but not by K191NSGK3. SGK3 was effective in the presence of ouabain (1 mM) and thus did not require Na+/K+ ATPase activity. Coexpression of Nedd4-2 decreased the voltage gated current in KCNA5 expressing Xenopus oocytes, an effect largely reversed by additional coexpression of SGK3.
  
  
  CONCLUSIONS
  SGK3 is a positive regulator of KCNA5, which is at least partially effective by abrogating the effect of Nedd4-2.
authors.affiliation: Department of Physiology I, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
authors.forename: Musaab
authors.initials: M
authors.lastname: Ahmed
authors.forename: Myriam
authors.initials: M
authors.lastname: Fezai
authors.forename: Nestor L
authors.initials: NL
authors.lastname: Uzcategui
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D000075702:Nedd4 Ubiquitin Protein Ligases; D009865:Oocytes / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018075:RNA, Complementary / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000254:growth & development / Q000378:metabolism; D029867:Xenopus Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D051666:Kv1.5 Potassium Channel; D000075702:Nedd4 Ubiquitin Protein Ligases; D010042:Ouabain; D017346:Protein Serine-Threonine Kinases; D018075:RNA, Complementary; D044767:Ubiquitin-Protein Ligases; D029867:Xenopus Proteins; C000618482:Nedd4 protein, Xenopus; C000618461:Nedd4l protein, mouse; C000618460:nedd4l protein, Xenopus; C523602:Sgk3 protein, mouse; D000099184:Serum-Glucocorticoid Regulated Kinases