DIRECT ACTIVATION OF THE OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNEL THROUGH MODIFICATION OF SULFHYDRYL-GROUPS BY NO COMPOUNDS

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.