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Department of Molecular Physiology

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olfaction
Cyclic nucleotide - gated cation channels

The cAMP-gated cation channels contain three distinct subunits: CNGA2, CNGA4, and CNGB1b. CNGA2 is able to form functional homomeric channels when expressed in cultured cells without the other subunits. In native cells, however, such A2 channels donīt exist. In olfactory neurons, CNGA2 co-assembles with A4 and B1b to form a heteromeric channel - probably with two A2 subunits and one each of the others. The three subunits are fairly similar, having six transmembrane regions, a cAMP-binding site within the carboxy terminus, and a region that contributes to the lining of the channel pore. However, there are some differences which are important for the physiological function of the channel. These concern channel activation by cAMP and channel inibition by calmodulin.

The cAMP dose-resonse curves on the right illustrate that A2 homomeric channels have a much lower cAMP sensitivity than native channels from OSNs or heteromeric A2A4B1b channels expressed in cultured cells. Thus, the channel needs all its subunits to respond to low concentrations of cAMP.

The other diagram shows the time course of channel inhibition by calmodulin (CaM). Inhibition of A2 channels is very slow, taking much more than a minute to develop completely. In contrast, the complete channel is inhibited within 1 - 3 seconds. This fast channel inhibition is necessary for olfaction because it is the basis of fast adaptation in OSNs - and it also requires all three subunits.



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