Concentration Dependence of Sodium Permeation and Sodium Ion Interactions in the Cyclic AMP-gated Channels of Mammalian Olfactory Receptor Neurons

1997 ◽  
Vol 159 (1) ◽  
pp. 41-52 ◽  
Author(s):  
S. Balasubramanian ◽  
J.W. Lynch ◽  
P.H. Barry
1993 ◽  
Vol 69 (5) ◽  
pp. 1758-1768 ◽  
Author(s):  
F. Zufall ◽  
S. Firestein

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.


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.


2009 ◽  
Vol 102 (4) ◽  
pp. 2121-2130 ◽  
Author(s):  
Hadas Lapid ◽  
Han-Seok Seo ◽  
Benno Schuster ◽  
Elad Schneidman ◽  
Yehudah Roth ◽  
...  

Electroolfactograms (EOGs) are the summated generator potentials of olfactory receptor neurons measured directly from the olfactory epithelium. To validate the sensory origin of the human EOG, we set out to ask whether EOGs measured in humans were odorant concentration dependent. Each of 22 subjects (12 women, mean age = 23.3 yr) was tested with two odorants, either valeric acid and linalool ( n = 12) or isovaleric acid and l-carvone ( n = 10), each delivered at four concentrations diluted with warm (37°C) and humidified (80%) odorless air. In behavior, increased odorant concentration was associated with increased perceived intensity (all F > 5, all P < 0.001). In EOG, increased odorant concentration was associated with increased area under the EOG curve (all F > 8, all P < 0.001). These findings substantiate EOG as a tool for probing olfactory coding directly at the level of olfactory receptor neurons in humans.


1994 ◽  
Vol 195 (1) ◽  
pp. 307-328 ◽  
Author(s):  
S J Kleene ◽  
R C Gesteland ◽  
S H Bryant

Individual olfactory receptor neurons vary widely in their responses to odorants. Olfactory stimulus reception occurs in the cilia of the receptor neurons. Thus, the variability among individual neurons could in part be due to differences among the olfactory cilia. We have quantified the known conductance properties of each of 117 frog olfactory cilia. From a strictly qualitative viewpoint, the cilia were very homogeneous. All but a few of them had a basal conductance in the absence of odorants and second messengers, conductances stimulated by cytoplasmic cyclic AMP and by Ca2+ and a conductance measured in the presence of ATP and stimulated by GTP gamma S. However, the magnitudes of the conductances varied widely among the cilia. Amplitudes of the cyclic-AMP- and Ca(2+)-activated ciliary currents correlated strongly with one another across the 117 cilia and 24 frogs studied, suggesting that expression of the underlying channels may be co-regulated. None of the conductance properties correlated strongly with ciliary length, a marker of cell maturity. Given cytoplasmic MgATP as substrate, ciliary adenylate cyclase apparently produced cyclic AMP, which in turn gated membrane channels and increased the ciliary conductance. In some cilia, MgATP alone caused a very large increase in conductance. In others, there was little effect unless GTP gamma S, which increases cyclase activity, was also added. No effect of cytoplasmic inositol trisphosphate on ciliary conductance was detectable.


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