scholarly journals Inhibitory signaling in mammalian olfactory transduction potentially mediated by Gαo

2019 ◽  
Author(s):  
Elizabeth A. Corey ◽  
Kirill Ukhanov ◽  
Yuriy V. Bobkov ◽  
Jeremy C. McIntyre ◽  
Jeffrey R. Martens ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Olfactory Receptor Neurons ◽  
Dependent Manner ◽  
Olfactory Transduction ◽  
Interesting Possibility ◽  
Dependent Inhibition ◽  
Receptor Neurons ◽  
Nucleotide Signaling ◽  
Phosphoinositide 3 Kinase ◽  
Inhibitory Signaling

AbstractOlfactory GPCRs (ORs) in mammalian olfactory receptor neurons (ORNs) mediate excitation through the Gαs family member Gαolf. Here we tentatively associate a second G protein, Gαo, with inhibitory signalling in mammalian olfactory transduction by first showing that odor evoked phosphoinositide 3-kinase (PI3K)-dependent inhibition of signal transduction is absent in the native ORNs of mice carrying a conditional OMP-Cre based knockout of Gαo. We then identify an OR from native rat ORNs that are activated by octanol through cyclic nucleotide signaling and inhibited by citral in a PI3K-dependent manner. We show that the OR activates cyclic nucleotide signaling and PI3K signaling in a manner that reflects its functionality in native ORNs. Our findings lay the groundwork to explore the interesting possibility that ORs can interact with two different G proteins in a functionally identified, ligand-dependent manner to mediate opponent signaling in mature mammalian ORNs.

scholarly journals 3-Phosphoinositides Modulate Cyclic Nucleotide Signaling in Olfactory Receptor Neurons

Neuron ◽  
2002 ◽  
Vol 33 (5) ◽  
pp. 731-739 ◽  
Author(s):  
Marc Spehr ◽  
Christian H. Wetzel ◽  
Hanns Hatt ◽  
Barry W. Ache
Keyword(s):  
Cyclic Nucleotide ◽  
Olfactory Receptor ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons ◽  
Nucleotide Signaling

Divalent cations block the cyclic nucleotide-gated channel of olfactory receptor neurons

1993 ◽  
Vol 69 (5) ◽  
pp. 1758-1768 ◽  
Author(s):  
F. Zufall ◽  
S. Firestein
Keyword(s):  
Cyclic Amp ◽  
Calcium Channels ◽  
Cyclic Nucleotide ◽  
Olfactory Receptor ◽  
Single Channel ◽  
Divalent Cations ◽  
Olfactory Receptor Neurons ◽  
Gated Channel ◽  
Receptor Neurons ◽  
Single Channel Currents

1. The effects of external divalent cations on odor-dependent, cyclic AMP-activated single-channel currents from olfactory receptor neurons of the tiger salamander (Ambystoma tigrinum) were studied in inside-out membrane patches taken from dendritic regions of freshly isolated sensory cells. 2. Channels were reversibly activated by 100 microM cyclic AMP. In the absence of divalent cations, the channel had a linear current-voltage relation giving a conductance of 45 pS. With increasing concentrations of either Ca2+ or Mg2+ in the external solution, the channel displayed a rapid flickering behavior. At higher concentrations of divalent cations, the transitions were too rapid to be fully resolved and appeared as a reduction in mean unitary single-channel current amplitude. 3. This effect was voltage dependent, and on analysis was shown to be due to an open channel block by divalent ions. In the case of Mg2+, the block increased steadily with hyperpolarization. In contrast, for Ca2+ the block first increased with hyperpolarization and then decreased with further hyperpolarization beyond -70 mV, providing evidence for Ca2+ permeation of this channel. 4. This block is similar to that seen in voltage-gated calcium channels. Additionally, the cyclic nucleotide-gated channel shows some pharmacological similarities with L-type calcium channels, including a novel block of the cyclic nucleotide channel by nifedipine (50 microM). 5. Our results indicate that the sensory generator current simultaneously depends on the presence of the second messenger and on the membrane potential of the olfactory neuron.

Both External and Internal Calcium Reduce the Sensitivity of the Olfactory Cyclic-Nucleotide-Gated Channel to cAMP

1999 ◽  
Vol 81 (6) ◽  
pp. 2675-2682 ◽  
Author(s):  
Steven J. Kleene
Keyword(s):  
Cyclic Nucleotide ◽  
Olfactory Receptor ◽  
Electrical Signal ◽  
Olfactory Receptor Neurons ◽  
Unexpected Result ◽  
Patch Clamp Recording ◽  
Ciliary Membrane ◽  
Gated Channel ◽  
Receptor Neurons ◽  
Internal Calcium

Both external and internal calcium reduce the sensitivity of the olfactory cyclic-nucleotide-gated channel to cAMP. In vertebrate olfaction, odorous stimuli are first transduced into an electrical signal in the cilia of olfactory receptor neurons. Many odorants cause an increase in ciliary cAMP, which gates cationic channels in the ciliary membrane. The resulting influx of Ca2+ and Na+ produces a depolarizing receptor current. Modulation of the cyclic-nucleotide-gated (CNG) channels is one mechanism of adjusting olfactory sensitivity. Modulation of these channels by divalent cations was studied by patch-clamp recording from single cilia of frog olfactory receptor neurons. In accord with previous reports, it was found that cytoplasmic Ca2+ above 1 μM made the channels less sensitive to cAMP. The effect of cytoplasmic Ca2+ was eliminated by holding the cilium in a divalent-free cytoplasmic solution and was restored by adding calmodulin (CaM). An unexpected result was that external Ca2+ could also greatly reduce the sensitivity of the channels to cAMP. This reduction was seen when external Ca2+ exceeded 30 μM and was not affected by the divalent-free solution, by CaM, or by Ca2+ buffering. The effects of cytoplasmic and external Ca2+ were additive. Thus the effects of cytoplasmic and external Ca2+ are apparently mediated by different mechanisms. There was no effect of CaM on a Ca2+-activated Cl− current that also contributes to the receptor current. Increases in Ca2+ concentration on either side of the ciliary membrane may influence olfactory adaptation.

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