Adaptation is a fundamental property of sensory systems that allows a living organism to adjust to ongoing changes in its environment by decreasing its sensitivity to persistent stimuli. In C. elegansAWA and AWC are responsible for sensation of a wide range of attractive volatile odors. Odor exposure for a prolonged time leads to reversible decreases in the animal''s attraction to odor (Colbert and Bargmann, 1995;L''Etoile et al., 2002). The specificity of olfactory adaptation is determined by the feeding status of the animal. If a well-fed worm is exposed to benzaldehyde for 1hr it will ignore both benzaldehyde and isoamyl alcohol. In contrast a starved worm after benzaldehyde exposure will blunt only the response to benzaldehyde leaving the response to isoamyl alcohol intact (Colbert and Bargmann,1997). The TAX-4/TAX-2heterotetrameric cyclic nucleotide-gated channel (cNG) is required for AWC-mediated olfactory responses.TAX-4 is an alpha subunit that can form homomeric channels while TAX-2 is a beta subunit that requires TAX-4 to form a functional channel (Coburn andBargmann, 1996; Komatsu et al., 1999). C. elegansencodes two additional predicted alpha subunits CNG-1 and CNG-3 (Suk-Woo et al., 2004a; 2004b and L''Etoile 2004) and two additional predicted beta subunits Y76B12C.1 and C23H5.7 (L''Etoile, 2004 andCara Coburn, thesis). In mice the olfactory channel is comprised of 3 alpha subunits: 2XCNGA2, 1XCNGA4 and the beta subunit CNGB1b. Like TAX-4,CNGA2 can homomerize but CNGA4 is required for both odor-sensitivity and adaptation to background odors (Munger et al., 2001; Kelliher et al., 2003).The function of CNG-1 and CNG-3 in behavior is unknown. Here we report that though both
cng-1 and
cng-3 mutants are wild-type in their response to a dilution series of AWC-sensed odors, CNG-3 is required in AWC for short-term adaptation to benzaldehyde and butanone. The
cng-1 mutant mimics a starved worm in that benzaldehyde exposure leads to adaptation of only the benzaldehyde response and spares the response to isoamyl alcohol. When we examined the subunits in HEK cells we found that like the mammalian alternate olfactory cNG alpha subunit CNG4A neither CNG-1 nor CNG-3 can homomerize to form a functional channel and yet each modulates the electrophysiological response of TAX-2 and TAX-4 heteromers to cGMP. CNG-1 lengthens the time constant for the channel closing in response to removal of cGMP. Since cGMP levels have been shown to decrease upon odor-exposure (Chalasani et al., 2007), we speculate that
cng-3 mutant worms (equivalent to TAX-2/4/CNG-1 expression in HEK cells) would be defective in saturation assays to the same odor. TheTAX-2/4/CNG-3 channel has very similar properties to that of the TAX-2/4channel. We are currently investigating native channel conformations in C.elegans using FRET and in Xenopus oocytes using TIRF microscopy (Ulbrich and Isacoff,2007)