Cyclic AMP Cascade Mediates the Inhibitory Odor Response of Isolated Toad Olfactory Receptor Neurons

2005 ◽  
Vol 94 (3) ◽  
pp. 1781-1788 ◽  
Author(s):  
Rodolfo Madrid ◽  
Ricardo Delgado ◽  
Juan Bacigalupo
Keyword(s):  
Cyclic Amp ◽  
Olfactory Receptor ◽  
Membrane Conductance ◽  
Receptor Potential ◽  
Olfactory Receptor Neurons ◽  
Direct Role ◽  
Olfactory Neurons ◽  
Pharmacological Agents ◽  
Receptor Neurons ◽  
20 Nm

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.

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.

scholarly journals Chemosensory responses in isolated olfactory receptor neurons from Necturus maculosus.

1992 ◽  
Vol 99 (3) ◽  
pp. 415-433 ◽  
Author(s):  
V E Dionne
Keyword(s):  
Olfactory Receptor ◽  
Membrane Conductance ◽  
Input Resistance ◽  
Primary Response ◽  
Olfactory Receptor Neurons ◽  
Whole Cell ◽  
Whole Cell Recording ◽  
Necturus Maculosus ◽  
Cell Recording ◽  
Receptor Neurons

Olfactory receptor neurons were isolated without enzymes from the mudpuppy, Necturus maculosus, and tested for chemosensitivity. The cells responded to odorants with changes in firing frequency and alterations in excitability that were detected with tight-seal patch electrodes using on-cell and whole-cell recording conditions. Chemosensitive cells exhibited two primary response characteristics: excitation and inhibition. Both types of primary response were observed in different cells stimulated by mixtures of amino acids as well as by the single compound L-alanine, suggesting that there may be more than one transduction pathway for some odorants. Using the normal whole-cell recording method, the chemosensitivity of competent cells washed out rapidly; a resistive whole-cell method was used to record odorant responses under current-clamp conditions. In response to chemical stimulation, excitability appeared to be modulated in several different ways in different cells: odorants induced hyperpolarizing or depolarizing receptor potentials, elicited or inhibited transient, rhythmic generator potentials, and altered excitability without changing the membrane potential or input resistance. These effects suggest that olfactory transduction is mediated through at least three different pathways with effects on four or more components of the membrane conductance. Polychotomous pathways such as these may be important for odor discrimination and for sharpening the "odor image" generated in the olfactory epithelium.

Transduction diversity in olfaction.

1994 ◽  
Vol 194 (1) ◽  
pp. 1-21 ◽  
Author(s):  
V E Dionne ◽  
A E Dubin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Olfactory Receptor ◽  
Membrane Conductance ◽  
Chemical Signals ◽  
Odor Discrimination ◽  
Olfactory Receptor Neurons ◽  
Electrophysiological Recordings ◽  
The Central Nervous System ◽  
Receptor Neurons

Odors are powerful stimuli that can focus the attention, elicit behaviors (or misbehaviors) and even resurrect forgotten memories. These actions are directed by the central nervous system, but they depend upon the initial transduction of chemical signals by olfactory receptor neurons. Electrophysiological recordings suggest that the responses of olfactory receptor neurons to odors are more diverse than was initially believed, being mediated by effects on several different conductances. Both excitatory and inhibitory responses are produced by these effects and some, if not all, odors can affect more than one component of the membrane conductance. The extent of this diversity is reviewed here, and its impact on our understanding of odor discrimination is discussed.

scholarly journals Voltage- and Ca(2+)-gated currents in zebrafish olfactory receptor neurons.

1996 ◽  
Vol 199 (5) ◽  
pp. 1115-1126 ◽  
Author(s):  
F S Corotto ◽  
D R Piper ◽  
N Chen ◽  
W C Michel
Keyword(s):  
Olfactory Receptor ◽  
Receptor Potential ◽  
Cell Voltage ◽  
Olfactory Receptor Neurons ◽  
Peak Amplitude ◽  
Delayed Rectifier ◽  
Maximal Conductance ◽  
Outward Currents ◽  
K Current ◽  
Receptor Neurons

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.

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
Keyword(s):  
Signal Transduction ◽  
Olfactory Receptor ◽  
Time Course ◽  
Olfactory Receptor Neurons ◽  
Delayed Rectifier ◽  
Ion Permeation ◽  
Olfactory Neurons ◽  
Receptor Neurons ◽  
Stimulation Of ◽  
Ion Conductances

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.

scholarly journals Modulation of Cl-, K+, and nonselective cation conductances by taurine in olfactory receptor neurons of the mudpuppy Necturus maculosus.

1993 ◽  
Vol 101 (4) ◽  
pp. 469-485 ◽  
Author(s):  
A E Dubin ◽  
V E Dionne
Keyword(s):  
Olfactory Receptor ◽  
Membrane Conductance ◽  
Olfactory Receptor Neurons ◽  
Whole Cell ◽  
Necturus Maculosus ◽  
Cation Conductance ◽  
Receptor Neurons ◽  
Excitatory Responses ◽  
Cl Conductance

Odors are transduced by processes that modulate the membrane conductance of olfactory receptor neurons. Olfactory neurons from the aquatic salamander, Necturus maculosus, were acutely isolated without enzymes and studied with a resistive whole-cell method to minimize loss of soluble intracellular constituents. 55 of 224 neurons responded to the test compound taurine at concentrations between 10 nM and 100 microM. Four different conductance changes were elicited by taurine: an increased Cl- conductance (33%), an increased nonselective cation conductance (15%), a decreased Cl- conductance (15%), and a decreased K+ conductance (15%); in addition, responses too small to be characterized were elicited in some neurons. In most cases, taurine appeared to modulate only a single conductance in any particular cell. Modulation of each conductance was dose dependent, and each response ran down quickly in the normal whole-cell mode, presumably due to washout of a diffusible component in the transduction pathway. Modulation of taurine-sensitive conductances caused either inhibitory or excitatory responses. A similar diversity of responses in vivo would produce a complex pattern of electrical activity that could encode the identity and characteristics of an odor.

Excitation, inhibition, and suppression by odors in isolated toad and rat olfactory receptor neurons

2000 ◽  
Vol 279 (1) ◽  
pp. C31-C39 ◽  
Author(s):  
Magdalena Sanhueza ◽  
Oliver Schmachtenberg ◽  
Juan Bacigalupo
Keyword(s):  
Firing Rate ◽  
Olfactory Receptor ◽  
Receptor Potential ◽  
Cell Voltage ◽  
Underlying Mechanism ◽  
Olfactory Receptor Neurons ◽  
Action Potential Firing ◽  
Potential Firing ◽  
A Cell ◽  
Receptor Neurons

Vertebrate olfactory receptor neurons (ORNs) exhibit odor-induced increases in action potential firing rate due to an excitatory cAMP-dependent current. Fish and amphibian ORNs also give inhibitory odor responses, manifested as decreases in firing rate, but the underlying mechanism is poorly understood. In the toad, an odor-induced Ca2+-activated K+ current is responsible for the hyperpolarizing receptor potential that causes inhibition. In isolated ORNs, a third manner by which odors affect firing is suppression, a direct and nonspecific reduction of voltage-gated and transduction conductances. Here we show that in whole cell voltage-clamped toad ORNs, excitatory or inhibitory currents were not strictly associated to a particular odorant mixture. Occasionally, both odor effects, in addition to suppression, were concurrently observed in a cell. We report that rat ORNs also exhibit odor-induced inhibitory currents, due to the activation of a K+ conductance closely resembling that in the toad, suggesting that this conductance is widely distributed among vertebrates. We propose that ORNs operate as complex integrator units in the olfactory epithelium, where the first events in the process of odor discrimination take place.

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