Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits

Calcium (Ca(2+)) influx through Ca(2+)-permeable ion channels plays a pivotal role in a variety of neuronal signaling processes, and negative-feed back control of this influx by Ca(2+) itself is often equally important for modulation of such signaling. Negative modulation by Ca(2+) through calmodulin (CaM) on cyclic nucleotide-gated (CNG) channels underlies the adaptation of olfactory receptor neurons to odorants. We show that this feedback requires two additional subunits of the native olfactory channel, CNGA4 and CNGB1b, even though the machinery for CaM binding and modulation is present in the principal subunit CNGA2. This provides a rationale for the presence of three distinct subunits in the native olfactory channel and underscores the subtle link between the molecular make-up of an ion channel and the physiological function it subserves.