Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons

Nature. 1994 Apr 7;368(6471):545-8. doi: 10.1038/368545a0.


Olfactory receptor neurons depolarize in response to odorant stimulation of their sensory cilia. One transduction mechanism involves a G-protein-mediated increase in adenylate cyclase activity, raising the internal cyclic AMP concentration to open a cyclic nucleotide-activated cation channel on the plasma membrane. An influx of Ca2+ through this channel, which is permeable to both monovalent and divalent cations, triggers olfactory adaptation. Previous work has indicated that at least part of this Ca(2+)-mediated adaptation resides in the channel itself, but the mechanism remains unclear and controversial. Here we use the cloned channel from rat expressed in a cell line and the native channel from rat olfactory receptor cells to show that Ca2+ reduces the apparent affinity of the channel for cAMP by up to 20-fold in the presence of calmodulin, an abundant protein in olfactory cilia. This decrease in apparent affinity appears to involve a direct interaction between Ca(2+)-calmodulin and the channel, and it can reduce the activation of the channel by cAMP by up to a few hundred-fold, suggesting that it may be a key component of the Ca(2+)-triggered olfactory adaptation.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Female
  • Ion Channels / metabolism*
  • Membrane Potentials
  • Nucleotides, Cyclic / metabolism*
  • Olfactory Receptor Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Calmodulin
  • Ion Channels
  • Nucleotides, Cyclic
  • Cyclic AMP
  • Cyclic GMP
  • Calcium