Research ArticleBiophysics

Differential Regulation by Cyclic Nucleotides of the CNGA4 and CNGB1b Subunits in Olfactory Cyclic Nucleotide–Gated Channels

Science Signaling  10 Jul 2012:
Vol. 5, Issue 232, pp. ra48
DOI: 10.1126/scisignal.2003110

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Unraveling Regulation of Olfactory CNG Channels by Cyclic Nucleotides

Heterotetrameric olfactory cyclic nucleotide–gated (CNG) channels undergo complex regulation by cyclic nucleotides cAMP and cGMP, with activation in response to binding to the CNGA2 subunit well established. Nache et al. used a fluorescent cGMP (fcGMP) analog and confocal patch-clamp fluorometry, which allows simultaneous analysis of ligand binding and channel activity, to explore channel regulation in response to ligand binding. Analysis of heterotetrameric channels containing various combinations of the CNGA4, CNGB1b, and CNGA2 subunits, with and without mutations that compromised cyclic nucleotide binding, showed that both the CNGA4 and the CNGA2 subunits, but not the CNGB1b subunit, bound and activated the channel in response to fcGMP. In contrast, all three subunits contributed to channel activation by cAMP. Thus, the presence of the CNGB1b subunit may enable the channel to discriminate between cAMP and cGMP.