Subunit configuration of heteromeric cone cyclic nucleotide-gated channels

Neuron. 2004 May 13;42(3):401-10. doi: 10.1016/s0896-6273(04)00225-9.


Cone photoreceptor cyclic nucleotide-gated (CNG) channels are thought to be tetrameric assemblies of CNGB3 (B3) and CNGA3 (A3) subunits. We have used functional and biochemical approaches to investigate the stoichiometry and arrangement of these subunits in recombinant channels. First, tandem dimers of linked subunits were used to constrain the order of CNGB3 and CNGA3 subunits; the properties of channels formed by B3/B3+A3/A3 dimers, or A3/B3+B3/A3 dimers, closely resembled those of channels arising from B3+A3 monomers. Functional markers in B3/B3 (or A3/A3) dimers confirmed that both B3 subunits (and both A3 subunits) gained membership into the pore-forming tetramer and that like subunits were positioned adjacent to each other. Second, chemical crosslinking and co-immunoprecipitation studies using epitope-tagged monomer subunits both demonstrated the presence of two CNGB3 subunits in cone channels. Together, these data support a preferred subunit arrangement for cone CNG channels (B3-B3-A3-A3) that is distinct from the 3A:1B configuration of rod channels.

Publication types

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

MeSH terms

  • Animals
  • Cyclic GMP / pharmacology
  • Cyclic Nucleotide-Gated Cation Channels
  • Diltiazem / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Ion Channels / biosynthesis
  • Ion Channels / chemistry*
  • Ion Channels / genetics
  • Protein Subunits / biosynthesis
  • Protein Subunits / chemistry*
  • Protein Subunits / genetics
  • Retinal Cone Photoreceptor Cells / chemistry*
  • Retinal Cone Photoreceptor Cells / drug effects
  • Retinal Cone Photoreceptor Cells / metabolism
  • Xenopus laevis


  • CNGB3 protein, human
  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • Protein Subunits
  • Diltiazem
  • Cyclic GMP