Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation

Alex Cheong, Andrew J Bingham, Jing Li, Bhaskar Kumar, Piruthivi Sukumar, Christopher Munsch, Noel J Buckley, Craig B Neylon, Karen E Porter, David J Beech, Ian C Wood

Research output: Contribution to journalArticlepeer-review


Induction of KCa3.1 (IKCa) potassium channel plays an important role in vascular smooth muscle cell proliferation. Here, we report that the gene encoding KCa3.1 (KCNN4) contains a functional repressor element 1-silencing transcription factor (REST or NRSF) binding site and is repressed by REST. Although not previously associated with vascular smooth muscle cells, REST is present and recruited to the KCNN4 gene in situ. Significantly, expression of REST declines when there is cellular proliferation, showing an inverse relationship with functional KCa3.1. Downregulated REST and upregulated KCa3.1 are also evident in smooth muscle cells of human neointimal hyperplasia grown in organ culture. Furthermore, inhibition of KCa3.1 suppresses neointimal formation, and exogenous REST reduces the functional impact of KCa3.1. Here, we show REST plays a previously unrecognized role as a switch regulating potassium channel expression and consequently the phenotype of vascular smooth muscle cells and human vascular disease.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalMolecular Cell
Issue number1
Publication statusPublished - 7 Oct 2005


  • Animals
  • Blood Vessels/metabolism
  • Cell Line
  • Cell Proliferation
  • Co-Repressor Proteins
  • DNA-Binding Proteins/genetics
  • Down-Regulation/physiology
  • Humans
  • Hyperplasia/metabolism
  • Intermediate-Conductance Calcium-Activated Potassium Channels/biosynthesis
  • Male
  • Mice
  • Myocytes, Smooth Muscle/metabolism
  • Nerve Tissue Proteins/genetics
  • Organ Culture Techniques/methods
  • Repressor Proteins/genetics
  • Response Elements/physiology
  • Up-Regulation/physiology


Dive into the research topics of 'Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation'. Together they form a unique fingerprint.

Cite this