title: Up-Regulation of Voltage Gated K+ Channels Kv1.3 and Kv1.5 by Protein Kinase PKB/Akt.
abstract: BACKGROUND
  The voltage gated K+ channels Kv1.3 and Kv1.5 contribute to the orchestration of cell proliferation. Kinases participating in the regulation of cell proliferation include protein kinase B (PKB/Akt). The present study thus explored whether PKB/Akt modifies the abundance and function of Kv1.3 and Kv1.5.
  
  
  METHODS
  Kv1.3 or Kv1.5 was expressed in Xenopus laevis oocytes with or without wild-type PKB/Akt, constitutively active T308D/S473DPKB/Akt or inactive T308A/S473APKB/Akt. The channel activity was quantified utilizing dual electrode voltage clamp. Moreover, HA-tagged Kv1.5 protein was determined utilizing chemiluminescence.
  
  
  RESULTS
  Voltage gated K+ currents were observed in Kv1.3 or Kv1.5 expressing oocytes but not in water-injected oocytes or in oocytes expressing PKB/Akt alone. Co-expression of PKB/Akt or T308D/S473DPKB/Akt, but not co-expression of T308A/S473APKB/Akt significantly increased the voltage gated current in both Kv1.3 and Kv1.5 expressing oocytes. As shown for Kv1.5, co-expression of PKB/Akt enhanced the channel protein abundance in the cell membrane. In Kv1.5 expressing oocytes voltage gated current decreased following inhibition of carrier insertion by brefeldin A (5 µM) to similarly low values in the absence and presence of PKB/Akt, suggesting that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane.
  
  
  CONCLUSIONS
  PKB/Akt up-regulates both, Kv1.3 and Kv1.5 K+ channels.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Warsi
authors.forename: Myriam
authors.initials: M
authors.lastname: Fezai
authors.forename: Mireia
authors.initials: M
authors.lastname: Fores
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015854:Up-Regulation; D014982:Xenopus laevis
chemical_list: D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051057:Proto-Oncogene Proteins c-akt