Ion channels and their molecular environments--glimpses and insights from functional proteomics

Semin Cell Dev Biol. 2011 Apr;22(2):132-44. doi: 10.1016/j.semcdb.2010.09.015. Epub 2010 Oct 8.


There is emerging evidence from functional analyses and molecular research that the role of ion channels in cell physiology is not only determined by the pore-forming subunits but also depends on their molecular environment. Accordingly, the local and temporal specificity of channel-mediated signal transduction is thought to result from association of these integral membrane proteins with distinct sets of partner proteins or from their assembly into stable macromolecular complexes. As yet, however, the molecular environments of most ion channels have escaped direct investigation, mostly because of technical limitations that precluded their comprehensive molecular analysis. Recent advances in proteomic technologies promoted an experimental workflow that combines affinity purification of readily solubilized protein complexes with quantitative high-resolution mass spectrometry and that offers access to channel-associated protein environments. We will discuss advantages and limitations of this proteomic approach, as well as the results obtained from its application to several types of ion channels including Cav channels, Kv channels, HCN channels, AMPA-type glutamate receptors and GABA(B) receptors. The respective results indicate that the approach provides unbiased and comprehensive information on (i) the subunit composition of channel cores including identification of auxiliary subunits, on (ii) the assembly of channel cores into 'signaling entities' and on (iii) integration of channels into extended protein networks. Thus, quantitative proteomics opens a new window for the investigation of ion channels and their function in the context of various types of cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatography, Affinity
  • Humans
  • Ion Channels / isolation & purification
  • Ion Channels / metabolism*
  • Mass Spectrometry
  • Protein Binding
  • Proteomics
  • Signal Transduction


  • Ion Channels