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Published September 13, 1994 | Published
Journal Article Open

Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP

Abstract

Olfactory receptor neurons respond to odorant stimulation with a rapid increase in intracellular cAMP that opens cyclic nucleotide-gated (cng) cation channels. cng channels in rat olfactory neurons are activated by cAMP in the low micromolar range and are outwardly rectifying. The cloned rat olfactory cng channel (rOCNC1), however, is much less sensitive to cAMP and exhibits very weak rectification. Here we describe the cloning and characterization of a second rat cng channel subunit, denoted rOCNC2. rOCNC2 does not form functional channels when expressed alone. When rOCNC1 and rOCNC2 are coexpressed, however, an outwardly rectifying cation conductance with cAMP sensitivity near that of the native channel is observed. In situ hybridization with probes specific for the two subunits shows that they are coexpressed in olfactory receptor neurons. These data indicate that the native olfactory cng channel is likely to be a heterooligomer of the rOCNC1 and rOCNC2 subunits.

Additional Information

Copyright © 1994 by the National Academy of Sciences. Contributed by Norman Davidson, May 20, 1994. We thank T.-Y. Chen and K.-W. Yau for helpful discussions, HEK 293 cells, and an rOCNC1 clone; W. Zagotta for providing the sequences of the CN1 and CN2 primers; Genentech for the pCIS plasmid; M. Quick and Y. Uezono of Caltech for experimental contributions to the early phase of this project; and L. Buck and E. Liman for communicating data before publication. J.B. was supported by a National Institutes of Health graduate training grant and an Achievement Award for College Scientists. This work was supported by grants from the National Institute of Mental Health and the National Institutes of Health to K.Z., H.A.L., and N.D.

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