Mc. Broillet et S. Firestein, DIRECT ACTIVATION OF THE OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNEL THROUGH MODIFICATION OF SULFHYDRYL-GROUPS BY NO COMPOUNDS, Neuron, 16(2), 1996, pp. 377-385
The activation of a cyclic nucleotide-gated channel is the final step
in sensory transduction in olfaction. Normally, this channel is opened
by the intracellular cyclic nucleotide second messenger cAMP or cGMP.
However, in single channel recordings we found that donors of nitric
oxide, a putative intercellular messenger, could directly activate the
native olfactory neuron channel. Its action was independent of the pr
esence of the normal ligand and did not involve the cyclic nucleotide
binding site, suggesting an alternate site on the molecule that is cri
tical in channel gating. The biochemical pathway appears to utilize ni
tric oxide in one of its alternate redox states, the nitrosonium ion,
transnitrosylating a free sulfhydryl group belonging to a cysteine res
idue tentatively identified as being in the region linking the S6 tran
smembrane domain to the ligand binding domain.