Odorants Suppress a Voltage-Activated K+ Conductance in Rat Olfactory Neurons

1999 ◽  
Vol 82 (1) ◽  
pp. 226-236 ◽  
Author(s):  
Fritz W. Lischka ◽  
John H. Teeter ◽  
Diego Restrepo

Stimulation of olfactory receptor neurons (ORNs) with odors elicits an increase in the concentration of cAMP leading to opening of cyclic nucleotide-gated (CNG) channels and subsequent depolarization. Although opening of CNG channels is thought to be the main mechanism mediating signal transduction, modulation of other ion conductances by odorants has been postulated. To determine whether K+ conductances are modulated by odorants in mammalian ORNs, we examined the response of rat ORNs to odors by recording membrane current under perforated-patch conditions. We find that rat ORNs display two predominant types of responses. Thirty percent of the cells responded to odorants with activation of a CNG conductance. In contrast, in 55% of the ORNs, stimulation with odorants inhibited a voltage-activated K+ conductance ( I Ko). In terms of pharmacology, ion permeation, outward rectification, and time course for inactivation, I Ko resembled a delayed rectifier K+ conductance. The effect of odorants on I Ko was specific (only certain odorants inhibited I Ko in each ORN) and concentration dependent, and there was a significant latency between arrival of odorants to the cell and the onset of suppression. These results indicate that indirect suppression of a K+ conductance ( I Ko) by odorants plays a role in signal transduction in mammalian ORNs.

1993 ◽  
Vol 123 (4) ◽  
pp. 963-976 ◽  
Author(s):  
Y Nemoto ◽  
J Ikeda ◽  
K Katoh ◽  
H Koshimoto ◽  
Y Yoshihara ◽  
...  

R2D5 is a mouse monoclonal antibody that labels rabbit olfactory receptor neurons. Immunoblot analysis showed that mAb R2D5 recognizes a 22-kD protein with apparent pI of 4.8, which is abundantly contained in the olfactory epithelium and the olfactory bulb. We isolated cDNA for R2D5 antigen and confirmed by Northern analysis and neuronal depletion technique that R2D5 antigen is expressed predominantly, but not exclusively, in olfactory receptor neurons. Analysis of the deduced primary structure revealed that R2D5 antigen consists of 189 amino acids with calculated M(r) of 20,864 and pI of 4.74, has three calcium-binding EF hands, and has possible phosphorylation sites for Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and cAMP-dependent protein kinase (A kinase). Using the bacterially expressed protein, we directly examined the biochemical properties of R2D5 antigen. R2D5 antigen binds Ca2+ and undergoes a conformational change in a manner similar to calmodulin. R2D5 antigen is phosphorylated in vitro by CaM kinase II and A kinase at different sites, and 1.81 and 0.80 mol of Pi were maximally incorporated per mol of R2D5 antigen by CaM kinase II and A kinase, respectively. Detailed immunohistochemical study showed that R2D5 antigen is also expressed in a variety of ependymal cells in the rabbit central nervous system. Aside from ubiquitous calmodulin, R2D5 antigen is the first identified calcium-binding protein in olfactory receptor neurons that may modulate olfactory signal transduction. Furthermore our results indicate that olfactory receptor neurons and ependymal cells have certain signal transduction components in common, suggesting a novel physiological process in ependymal cells.


2019 ◽  
Vol 16 (157) ◽  
pp. 20190246 ◽  
Author(s):  
Marie Levakova ◽  
Lubomir Kostal ◽  
Christelle Monsempès ◽  
Philippe Lucas ◽  
Ryota Kobayashi

In order to understand how olfactory stimuli are encoded and processed in the brain, it is important to build a computational model for olfactory receptor neurons (ORNs). Here, we present a simple and reliable mathematical model of a moth ORN generating spikes. The model incorporates a simplified description of the chemical kinetics leading to olfactory receptor activation and action potential generation. We show that an adaptive spike threshold regulated by prior spike history is an effective mechanism for reproducing the typical phasic–tonic time course of ORN responses. Our model reproduces the response dynamics of individual neurons to a fluctuating stimulus that approximates odorant fluctuations in nature. The parameters of the spike threshold are essential for reproducing the response heterogeneity in ORNs. The model provides a valuable tool for efficient simulations of olfactory circuits.


1997 ◽  
Vol 200 (11) ◽  
pp. 1571-1586
Author(s):  
M T Lucero ◽  
N Chen

We performed whole-cell voltage-clamp experiments on isolated olfactory neurons from the squid Lolliguncula brevis. Total outward currents were composed of three identifiable K+ currents: a delayed rectifier K+ current that showed slow inactivation and was sensitive to 5 mmol l-1 tetraethylammonium; a rapidly inactivating, 4-aminopyridine (4-AP)-sensitive, A-type K+ current and a Ca(2+)-sensitive K+ current that was blocked by 200 nmol l-1 charybdotoxin and 10 mmol l-1 Cd2+ but was insensitive to apamin. The proportion of each current type varied from cell to cell, suggesting that responses to a given odorant would depend of the complement of channels present. The kinetics of the K+ currents were affected by temperature, with Q10 values ranging from 2 to 6. The identification and characterization of these K+ currents will greatly aid our understanding of action potential generation in these cells and will facilitate modelling of how odor responses are transduced and coded in squid olfactory receptor neurons.


2017 ◽  
Author(s):  
Vincent Jacob ◽  
Christelle Monsempès ◽  
Jean-Pierre Rospars ◽  
Jean-Baptiste Masson ◽  
Philippe Lucas

AbstractLong-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs) and antennal lobe projection neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m) from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear–nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.Author SummaryLong-distance olfactory search is a difficult task because atmospheric turbulence erases global gradients and makes the plume discontinuous. The dynamics of odor detections is the sole information about the position of the source. Male moths successfully track female pheromone plumes at large distances. Here we show that the moth olfactory system encodes olfactory scenes simulating variable distances from the odor source by characterizing puff onsets and offsets. A single projection neuron is sufficient to provide an accurate representation of the dynamic pheromone time course at any distance to the source while this information seems to be encoded at the population level in olfactory receptor neurons.


2005 ◽  
Vol 94 (3) ◽  
pp. 1781-1788 ◽  
Author(s):  
Rodolfo Madrid ◽  
Ricardo Delgado ◽  
Juan Bacigalupo

Odor stimulation may excite or inhibit olfactory receptor neurons (ORNs). It is well established that the excitatory response involves a cyclic AMP (cAMP) transduction mechanism that activates a nonselective cationic cyclic nucleotide-gated (CNG) conductance, accompanied by the activation of a Ca2+-dependent Cl− conductance, both causing a depolarizing receptor potential. In contrast, odor inhibition is attributed to a hyperpolarizing receptor potential. It has been proposed that a Ca2+-dependent K+ (KCa) conductance plays a key role in odor inhibition, both in toad and rat isolated olfactory neurons. The mechanism underlying odor inhibition has remained elusive. We assessed its study using various pharmacological agents and caged compounds for cAMP, Ca2+, and inositol 1,4,5-triphosphate (InsP3) on isolated toad ORNs. The odor-triggered KCa current was reduced on exposing the cell either to the CNG channel blocker LY83583 (20 μM) or to the adenylyl cyclase inhibitor SQ22536 (100 μM). Photorelease of caged Ca2+ activated a Cl− current sensitive to niflumic acid (10 μM) and a K+ current blockable by charybdotoxin (20 nM) and iberiotoxin (20 nM). In contrast, photoreleased Ca2+ had no effect on cells missing their cilia, indicating that these conductances are confined to the cilia. Photorelease of cAMP induced a charybdotoxin-sensitive K+ current in intact ORNs. Photorelease of InsP3 did not increase the membrane conductance of olfactory neurons, arguing against a direct role of InsP3 in chemotransduction. We conclude that a cAMP cascade mediates the activation of the ciliary Ca2+-dependent K+ current and that the Ca2+ ions that activate the inhibitory current enter the cilia through CNG channels.


2016 ◽  
Vol 113 (40) ◽  
pp. 11078-11087 ◽  
Author(s):  
Rong-Chang Li ◽  
Yair Ben-Chaim ◽  
King-Wai Yau ◽  
Chih-Chun Lin

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide–gated (CNG), nonselective cation channels. The consequent Ca2+ influx triggers adaptation but also signal amplification, the latter by opening a Ca2+-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose–response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca2+-activated Cl current does not influence the behavioral olfactory threshold in mice.


1996 ◽  
Vol 199 (5) ◽  
pp. 1115-1126 ◽  
Author(s):  
F S Corotto ◽  
D R Piper ◽  
N Chen ◽  
W C Michel

Voltage- and Ca(2+)-gated currents were recorded from isolated olfactory receptor neurons (ORNs) of the zebrafish Danio rerio using the whole-cell voltage-clamp technique. Zebrafish ORNs had an average capacitance of 0.66 pF and an average apparent input resistance of 8.0 G omega. Depolarizing steps elicited transient inward currents followed by outward currents with transient and sustained components. The transient inward current (INa) was sensitive to 1 mumol l-1 tetrodotoxin, activated between -74mV and -64mV, and reached half-maximal conductance at -28 mV. Its peak amplitude averaged -101pA. Steady-state inactivation of INa was half-maximal at an average test potential of -78mV and recovery from inactivation proceeded with two time constants averaging 23 ms and 532 ms. A sustained, Co(2+)-sensitive current (ICa) activated between -44mV and -34mV and reached a peak amplitude averaging -9pA at -14mV. Outward currents were carried by K+, based on the reversal potentials of tail currents, and consisted of a Ca(2+)-dependent K+ current, a delayed rectifier current (IDR) and a transient K+ current (IA). The Ca(2+)-dependent K+ current (IK(Ca)) activated between -44mV and -34mV, whereas IDR and IA activated between -34mV and -24mV. In summary, zebrafish ORNs possess a complement of gated currents similar but not identical to that of ORNs from other vertebrates and which appears well suited for encoding a graded receptor potential into a train of action potentials.


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