title: Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism.
abstract: OBJECTIVE
  Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of all voltage-dependent potassium channel (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation of Kv1.3 currents seems to be important to modulate proliferation of mice femoral vascular smooth muscle cells in culture. This study was designed to explore if these changes in Kv1 expression pattern constituted a landmark of phenotypic modulation across vascular beds and to investigate the mechanisms involved in the proproliferative function of Kv1.3 channels.
  
  
  RESULTS
  Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and aortic vascular smooth muscle cells, and their correlate with protein expression was electrophysiologicaly confirmed using selective blockers. Heterologous expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the proliferation rate. The proproliferative effect of Kv1.3 channels was reproduced by "poreless" mutants but disappeared when voltage-dependence of gating was suppressed.
  
  
  CONCLUSIONS
  These findings suggest that the signaling cascade linking Kv1.3 functional expression to cell proliferation is activated by the voltage-dependent conformational change of the channels without needing ion conduction. Additionally, the conserved upregulation of Kv1.3 on phenotypic modulation in several vascular beds makes this channel a good target to control unwanted vascular remodeling.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular, Universidad de Valladolid y CSIC, Valladolid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Cidad
authors.forename: Laura
authors.initials: L
authors.lastname: Jiménez-Pérez
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Arribas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Miguel-Velado
authors.forename: Sendoa
authors.initials: S
authors.lastname: Tajada
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz-McDavitt
authors.forename: José R
authors.initials: JR
authors.lastname: López-López
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pérez-García
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051664:Kv1.3 Potassium Channel / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D051664:Kv1.3 Potassium Channel; D012333:RNA, Messenger