Inhibition of the olfactory cyclic nucleotide gated ion channel by intracellular calcium

When olfactory receptor neurons are exposed to sustained application of odours, the elicited ionic current is transient. This adaptation-like effect appears to require the influx of Ca$^{2+}$ through the odour-sensitive conductance; in the absence of extracellular Ca$^{2+}$ the current remains sustained. Odour transduction proceeds through a G-protein-based second messenger system, resulting finally in the direct activation of an ion channel by cyclic AMP. This channel is one possible site for a negative feedback loop using Ca$^{2+}$ as a messenger. In recordings of single cyclic AMP gated channels from olfactory receptor neurons, the open probability of the channel in saturating cAMP concentrations was dependent on the concentration of intracellular Ca$^{2+}$. It could be reduced from 0.6 in 100 nM Ca$^{2+}$ to 0.09 in 3 $\mu $M Ca$^{2+}$. However, as neither the single channel conductance nor the mean open time were affected by Ca$^{2+}$ concentration, this does not appear to be a mechanism of simple channel block. Rather, these results suggest that intracellular Ca$^{2+}$ acts allosterically to stabilize a closed state of the channel.