From the Boston University Marine Program, Marine Biological Laboratory, Woods Hole, Massachusetts 02543
Odors seem the most subtle of sensory stimuli, yet our
ability to detect them is robust, and their capacity to influence our actions is profound. Although scientists
have studied olfaction for >2,000 yr, advances in understanding the cell physiology of odor detection have
occurred especially rapidly in the past decade since the
application of the patch clamp technique (Anderson
and Ache, 1985 At the cellular level, odors are detected by olfactory receptor neurons, a specialized kind of bipolar neuron that
is exposed at one end on the surface of the nasal epithelium and connected at the other end to the central nervous system by synapses in the olfactory bulb. When the
neurons detect odors in the nasal airway, they respond
with quick but transient changes in excitability, resulting
in a pattern of action potentials, encoding information about the odor and sending it directly to the brain.
At the molecular level, odor responses are produced by
G protein-coupled receptors that modulate the levels of
intracellular second messengers (Shepherd, 1994 The cyclic AMP-associated transduction current is
turned on with a latency of several hundred milliseconds after exposure to odor, and turned off over the
course of a second or so, typically outlasting brief odor
pulses. The long activation latency reflects the time
needed for the second messenger pathway to be activated, and each step along the activation pathway represents a potential regulatory site for endogenous control of the response. Processes such as modulation by
intracellular Ca/calmodulin of the affinity of the CNG
cation channel for cyclic AMP, and modulation by cyclic GMP of the kinetics of the CNG channel, regulate
the odor response by acting on the activation pathway.
In fact, the transduction current shows adaptation, rundown, hormonal modulation, and possibly other forms
of plasticity, attesting to the importance of regulation on neuronal excitability. Into the light of this emphasis
on the activation pathway step Reisert and Matthews
(1998) Like in other sensory systems, the mechanisms underlying olfactory transduction are becoming increasingly complex. Presumably, it is this complexity with its
inherent feedback and control pathways that helps insure the robustness of the olfactory response.
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; Trotier, 1986
). Important roles for G
protein-coupled receptors, intracellular messengers,
and certain ion channels in odor transduction were
demonstrated (for review see Schild and Restrepo,
1998
), and it seemed that the odor response might well
be regulated in its entirety by these components or
through modulation of them. Now, Reisert and Matthews (1998)
present evidence that a Na/Ca exchanger
appears to control the decline of the sensory transduction current in at least some frog olfactory receptor neurons. This observation extends the list of players
that have been implicated in odor transduction and introduces a novel and additional means for cells to manage the odor response.
). Several such pathways have been implicated in odor transduction, but by far the best studied is one that uses cyclic AMP. The cyclic AMP pathway is activated when odor
molecules bind to specific G protein-coupled receptors on the apical cilia of olfactory receptor neurons and,
through the action of a G protein, possibly GOLF, activate
type III adenylyl cyclase, thus elevating intracellular cAMP.
Cyclic AMP can bind to cyclic nucleotide-gated (CNG)
cation channels causing them to open; this channel,
which occurs at high density in the ciliary membrane of
many olfactory receptor neurons, is primarily permeable to Ca2+ under physiological conditions. Calcium influx
through the channel activates a secondary current carried by Cl
ions through Ca-gated Cl
channels; it is this
secondary current that produces most of the receptor
potential. Together, these primary and secondary conductances depolarize the olfactory neuron. In a high percentage of frog olfactory receptor neurons, cineole, a
fragrant extract from eucalyptus, reliably activates the cyclic AMP pathway; this was the experimental preparation
used by Reisert and Matthews (1998)
to study the mechanism of termination of the transduction current.
, who look at termination of the transduction
current. They show that termination of the current mirrors a decline in intracellular Ca2+ and conclude that
this decline is controlled by a Na/Ca exchange mechanism. This introduces a new player in the olfactory
arena and, possibly more importantly, a new mechanism whose regulation may explain additional forms of
modulation of odor transduction.
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REFERENCES |
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1. | Anderson, P.A.V., and B.W. Ache. 1985. Voltage- and current-clamp recordings of the receptor potential in olfactory receptor cells in situ. Brain Res 338: 273-280 [Medline]. |
2. |
Reisert, J., and
H.R. Matthews.
1998.
Na+-dependent Ca2+ extrusion governs response recovery in frog olfactory receptor cells.
J.
Gen. Physiol.
112:
529-535
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3. |
Schild, D., and
D. Restrepo.
1998.
Transduction mechanisms in
vertebrate olfactory receptor cells.
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429-466
|
4. | Shepherd, G.M.. 1994. Discrimination of molecular signals by the olfactory receptor neuron. Neuron 13: 771-790 [Medline]. |
5. | Trotier, D.. 1986. A patch-clamp analysis of membrane currents in salamander olfactory receptor cells. Pflügers Arch 407: 589-595 [Medline]. |