Chem. Senses 24: 701-704,
1999
© Oxford University Press 1999
Simulation Analysis of Effects of Adrenaline on Spike Generation in Olfactory Receptor Cells
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104-6058, USA and Department of Information Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
Correspondence to be sent to: Dr Fusao Kawai, 123 Anatomy/Chemistry Bldg, The Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA. e-mail:kawai{at}nips.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Adrenaline is known to affect action potentials induced by the step current injection in an olfactory receptor cell (ORC). It is unclear, however, whether it also modulates action potentials induced by odor stimuli. In the present study, the effects of adrenaline on action potentials in ORCs were investigated quantitatively using a computer simulation. Adrenaline suppressed simulated action potentials induced by step current injection near threshold, and increased spike frequency to strong stimuli by 8–25%. Similar effects were obtained by applying a pseudo-transduction current to a model cell. Surprisingly, adrenaline markedly increased spike frequency to strong stimuli by 30–140%, and increased the slope of the stimulus–response relation compared with that of the step current injection. This suggests that adrenaline enhances odorant contrast in olfactory perception by modulating signal encoding of ORCs.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Odorant binding to receptor proteins at the ciliary surface of olfactory receptor cells (ORCs) activates enzymatic cascades (Bakalyar and Read, 1991
; Breer
and Boekhoff, 1992), inducing
transduction currents (Gold and Nakamura, 1987; Firestein, 1992; Restrepo et al., 1996).
This initial excitation causes a slow and graded voltage change; its amplitude is dependent on odor
concentration (Firestein et al., 1993). A graded receptor potential is
then encoded into spike
trains that transmit olfactory information to the brain.
Olfactory sensitivities are influenced by adrenaline (Beidler, 1961; Arechiga and Alcocer, 1969;
Getchell and Getchell, 1984; Zielinski et al., 1989; Woodhead and Nimmo, 1991). Adrenaline
enhances the amplitude of the electro-olfactogram induced by an odorant (Arechiga and
Alcocer, 1969). Noradrenaline released from the sympathetic nerve also increases
electrical activity in the
olfactory nerve (Beidler, 1961). Using the patch-clamp technique, our group
showed that adrenaline
affects spike generation of ORCs by modulating the Na + current (INa) and
T-type Ca2+ current (ICa,T) via cAMP (Kawai et al., 1999). Adrenaline increased the slope of the stimulus–response relation for
action potentials
induced by step current injection. It is unclear, however, whether adrenaline also modulates action
potentials induced by odor stimuli, because the time course of the odor transduction current is much
slower than that of the step current (Gold and Nakamura, 1987; Kurahashi, 1989; Firestein et al., 1993); gradual
membrane depolarization induced by the slow transduction current might inactivate
transient inward currents such as INa and ICa,T.
It is known that application of odorants causes secondary effects by suppressing the voltage-gated
ionic currents nonselectively and action potentials in ORCs (Kawai et al., 1997a). Although
the IC50s of INa (110 µM) and ICa,T (150
µM) for amyl acetate are higher than the K1/2 (a halfmaximal concentration;
53 µM) of the transduction current (Kawai et al., 1997a; Firestein et al.,
1993), concentrations of amyl acetate which are lower than the K1/2
of the
transduction current suppress INa and ICa,T by
~5–20% (Kawai et al., 1997a). Thus, it is difficult to
investigate the effects of
adrenaline on action potentials induced by odorants (even at low concentrations) with the conventional
patch-clamp technique. In the present study, this effect was examined using an ionic current model of
ORCs.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
An ionic current model of ORCs proposed in our previous report [cf. Table 1 in (Kawai et al., 1997b
)] was used for the present
simulations. This model was constructed to describe its ionic
currents (Na+-, T-type Ca2+-, L-type Ca2+and delayed
rectifier K+ currents) by a program using differential equations similar to the method of
Hodgkin and Huxley (Hodgkin and Huxley, 1952). The model equations were
calculated on an
IBM-compatible PC by the method of Runge-Kutta (Hamming, 1962) (time
step, 10 µs) to give
voltage and current values. The conductance of Na+ or Ca2+ channels was
determined by the product of the activation parameter (m) and inactivation parameter (h), and that of the K+ channel was calculated only by the activation parameter (n). A transduction current induced by an odor stimulus was modeled by the alpha function
|
 | (1) |
where K is the peak current amplitude and t is the time constant. Since the time constant
of transduction current in newt ORCs is ~400 ms (Kurahashi, 1989), it was
approximated with t of 400 ms.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
I first examined the effects of adrenaline on action potentials induced by step current injection using the ORC model. Since adrenaline reduces the conductance of the T-type Ca2+ channel in newt ORCs by 33% and shifts the activation curve of the Na+ channel toward a negative voltage (–4 mV) (Kawai et al., 1999
), these effects
were incorporated into the ORC model. In the adrenaline condition, GCa,T in the
T-type Ca2+ current model (Table 1) was decreased by 33%,
and aNa_m and ßNa_m in the Na+ current model were
shifted to a negative voltage by 4 mV. Under weakly stimulated conditions (5 pA, Figure
1A), adrenaline suppressed simulated action potentials. To strong stimuli causing repetitive
spikes, adrenaline increased spike frequency (Figure 1B). Spike frequency
was increased by 8–25% between 10 and 15 pA (Figure 1C).
Adrenaline also narrowed the dynamic range and made the stimulus–response relation steeper (Figure 1C). Mean
slopes between 5 and 15 pA were 0.9 spikes• s–1•pA–1 in the control condition and 1.4 spikes•–1•pA–1 in the adrenaline condition. Adrenaline thus amplified the simulated signal by
~60%. These results are consistent with our previous experimental data (Kawai et al., 1999).
|
To investigate effects of adrenaline on action potentials induced by odor stimuli, a pseudo-transduction current at various amplitudes (Figure 2A) was injected into the ORC model. The pseudo-transduction current was approximated by alpha functions (see equation 1). Adrenaline also suppressed simulated action potentials induced by the current injection with a weak stimulation (5 pA, Figure 2B). In contrast, adrenaline increased spike frequency with a strong stimulation (10 pA, Figure 2C). Surprisingly, the increased ratio (30–140%) of adrenaline to the control condition between 8 and 15 pA (Figure 2D) was markedly larger than that (8–25%) obtained by the simulation of the step current injection (Figure 1C). Adrenaline also narrowed the dynamic range and made the simulated stimulus–response relation steeper. Mean slopes between 5 and 15 pA were 0.25 spikes•s–1•pA–1 in the control condition and 0.75 spikes•s–1•pA–1 in the adrenaline condition. Adrenaline thus amplified the signal by ~3-fold. This result suggests that the adrenergic system may work to enhance odorant contrast by modulating signal encoding of ORCs.
|
By using the ORC model, we can estimate ionic current responses to odor stimuli during the activation of action potentials. Figure 3A shows ICa,T and INa responses, when the pseudo-transduction current of 5 pA induced action potentials in the control condition (thin line in Figure 2B). ICa,T was activated faster (arrow in Figure 3A) than INa because the activation voltage of ICa,T in ORCs is more negative than that of INa (Kawai et al., 1996
). When the
pseudo-transduction current of 5 pA was injected into the model under the adrenaline condition, neither
ICa,T nor INa (data not shown) was activated during the
membrane potential change (thick line in Figure 2B). With the strong
stimulation (10 pA), adrenaline
increased the activation frequency of ICa,T and decreased its amplitude (data not
shown). In contrast, adrenaline increased both the activation frequency of INa and
its amplitude (Figure 3B). A similar result was obtained when the only ICa,T component was removed from the ORC model, suggesting that INa is responsible
for the increase of spike activity by adrenaline (Figure 2C).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
In the present study, the effects of adrenaline on the action potentials were studied using a computer simulation. The results of the simulated step current injection were almost consistent with those of the previous experiment (Kawai et al., 1999
). However,
there were slight differences
of the mean slope in the stimulus–response relation between the simulation (Figure
1C) and the
previous experiment [figure 1C in (Kawai et al., 1999)]. Adrenaline made the mean slope in
the experiment slightly steeper than that in the simulation. The reasons for these differences are unclear.
Recently, it has been shown that dopamine modulates a K+ current in rat ORCs via
cAMP (Vargas and Lucero, 1999). Since a ß-adrenergic receptor uses
cAMP as a second
messenger, adrenaline might also modulate K+ currents in newt ORCs and change their
spike activities.
Adrenaline may regulate vasomotor tone and secretion from the Bowman's glands,
which modulate odorant access to and clearance from the olfactory epithelium (Getchell
and Getchell,
1984; Zielinski et al., 1989; Chen et al., 1993). Although the present simulation does
not exclude this possibility, the modulation by adrenaline of spiking activities should be regarded as an
important effect of adrenaline. A 3-fold increase in the slope of the simulated intensity– response
relation for odor stimuli (Figure 2D) seems to be quite significant.
Consequently, ORCs can encode the
difference between the presence of an odor stimulus and its absence, since the amplitude of the
transduction current rises with the increase of odor concentration (Firestein et al.,
1993).
Under natural conditions this may contribute to improving the identification ability for the presence of
odorants.
|
Acknowledgments |
|---|
I thank Drs A. Kaneko, T. Kurahashi and R. Smith for their advice and discussion, and J. Demb for critical reading of the manuscript.
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Arechiga, C. and Alcocer, H. (1969) Adrenergic effects on electroolfactogram. Exp. Med. Surg., 27, 384–394.[ISI][Medline]
Bakalyar, H.A. and Reed, R.R. (1991) The second messenger cascade in olfactory receptor neurons. Curr. Opin. Neurobiol., 1, 204–208.[Medline]
Beidler, L.M. (1961) Sensory Communication. Wiley/MIT Press, New York.
Breer, H. and Boekhoff, I. (1992) Second messenger signalling in olfaction. Curr. Opin. Neurobiol., 2, 439–443.[Medline]
Chen, Y., Getchell, T.V, Sparks, D.L. and Getchell, M.L. (1993) Patterns of adrenergic and peptidergic innervation in human olfactory mucosa: age-related trends. J. Comp. Neurol., 334, 104–116.[ISI][Medline]
Firestein, S. (1992) Electrical signals in olfactory transduction. Curr. Biol., 2, 444–448.
Firestein, S., Picco, C. and Menini, A. (1993) The relation between stimulus and response in olfactory receptor cells of the tiger salamander. J. Physiol. (Lond.), 468, 1–10.
Getchell, M.L. and Getchell, T.V. (1984) ß-Adrenergic regulation of the secretory granule content of acinar cells in olfactory glands on the salamander. J. Comp. Neurol., 155, 435–443.
Gold, G.H. and Nakamura, T. (1987) Cyclic nucleotide-gated conductances: a new class of ionic channels mediates visual and olfactory transduction. Trends. Pharmacol., 8, 312–316.
Hamming, R.W. (1962) Numerical Methods for Scientists and Engineers. McGraw-Hill, New York.
Hodgkin, A.L. and Huxley, A.F. (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (Lond.), 117, 500–544.
Kawai, F., Kurahashi, T. and Kaneko, A. (1996) T-type Ca. 2+ channel lowers the threshold of spike generation in the newt olfactory receptor cell. J. Gen. Physiol., 108, 525–535.
Kawai, F., Kurahashi, T. and Kaneko, A. (1997a) Nonselective suppression of voltage-gated currents by odorants in the newt olfactory receptor cells. J. Gen. Physiol., 109, 265–272.
Kawai, F., Kurahashi, T. and Kaneko, A. (1997b) Quantitative analysis of Na. + and Ca. 2+current contributions on spike initiation in the newt olfactory receptor cell. Jpn. J. Physiol., 47, 367–376.
Kawai, F., Kurahashi, T. and Kaneko, A. (1999) Adrenaline enhances odorant contrast by modulating signal encoding in olfactory receptor cells. Nature Neurosci., 2, 133–138.[ISI][Medline]
Kurahashi, T. (1989) Activation by odorants of
cation-selective conductance in the olfactory receptor cells isolated from the newt. J.
Physiol. (Lond.), 419, 177–192.
Restrepo, D., Teeter, J.H. and Schild, D. (1996) Second messenger signaling in olfactory transduction. J. Neurobiol., 30, 37–48.[ISI][Medline]
Vargas, G. and Lucero, M.T. (1999) Dopamine modulates inwardly rectifying hyperpolarization-activated current (Ih) in cultured rat
olfactory receptor neurons. J. Neurophysiol, 81, 149–158.
Woodhead, C.J. and Nimmo, A.J. (1991) Beta adrenoceptors in human nasal mucosa. J. Laryngol. Otol., 105, 632–634.[Medline]
Zielinski, B.S., Getchell, M.L., Wenokur, R. L. and Getchell, T.V. (1989) Ultrastructural localization and identification of adrenergic and cholinergic nerve terminals in the olfactory mucosa. Anat. Rec., 225, 232–245.[Medline]
Accepted July 2, 1999
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||