Ca2+ permeation in cyclic nucleotide-gated channels

EMBO J. 1999 Jan 4;18(1):131-44. doi: 10.1093/emboj/18.1.131.


Cyclic nucleotide-gated (CNG) channels conduct Na+, K+ and Ca2+ currents under the control of cGMP and cAMP. Activation of CNG channels leads to depolarization of the membrane voltage and to a concomitant increase of the cytosolic Ca2+ concentration. Several polypeptides were identified that constitute principal and modulatory subunits of CNG channels in both neurons and non-excitable cells, co-assembling to form a variety of heteromeric proteins with distinct biophysical properties. Since the contribution of each channel type to Ca2+ signaling depends on its specific Ca2+ conductance, it is necessary to analyze Ca2+ permeation for each individual channel type. We have analyzed Ca2+ permeation in all principal subunits of vertebrates and for a principal subunit from Drosophila melanogaster. We measured the fractional Ca2+ current over the physiological range of Ca2+ concentrations and found that Ca2+ permeation is determined by subunit composition and modulated by membrane voltage and extracellular pH. Ca2+ permeation is controlled by the Ca2+-binding affinity of the intrapore cation-binding site, which varies profoundly between members of the CNG channel family, and gives rise to a surprising diversity in the ability to generate Ca2+ signals.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling
  • Cattle
  • Cell Line
  • Cell Membrane Permeability
  • Cyclic Nucleotide-Gated Cation Channels
  • Drosophila melanogaster
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Ion Channel Gating
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Kinetics
  • Membrane Potentials
  • Nucleotides, Cyclic / metabolism
  • Olfactory Receptor Neurons / metabolism
  • Protein Conformation
  • Rabbits
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection


  • Calcium Channels
  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • Nucleotides, Cyclic
  • Recombinant Proteins
  • Calcium