Photolysis of caged cyclic AMP in the ciliary cytoplasm of the newt olfactory receptor cell

Takeuchi, Hiroko; Kurahashi, Takashi

doi:10.1113/jphysiol.2002.016600

Cited by 44 publications

(76 citation statements)

References 37 publications

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“…Similarly, cytoplasmic photolysis of caged cAMP induced inward current responses with similar profiles as the odorant-induced current ( Fig. 1 D, E) (n H ϭ 5.1 Ϯ 1.9; n ϭ 21) (Takeuchi and Kurahashi, 2002). This indicates that the nonlinear amplification is established at the downstream point from the cAMP production and has been interpreted to be attributed to the involvements of two different transduction channels, namely, CNG channels and Ca 2ϩ -activated Cl Ϫ channels ( Fig.…”

Section: Resultsmentioning

confidence: 89%

“…Single receptor cells were enzymatically (0.1% collagenase) dissociated from the olfactory epithelium of the newt Cynops pyrrhogaster, as described previously (Kurahashi, 1989;Takeuchi and Kurahashi, 2002). Cells were bathed in the normal Ringer's solution containing the following (in mM): 110 NaCl, 3.7 KCl, 3 CaCl 2 , 1 MgCl 2 , 10 HEPES, 15 glucose, and 1 pyrvate, pH adjusted to 7.4 with NaOH, before use.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we used the following steps to estimate [cAMP] i and its time dependence within the cilia. First, the intensity-response relationship of light-induced responses was obtained to specify n H (5.1) (Takeuchi and Kurahashi, 2002). Second, light steps with different intensities were applied to obtain the light-induced current as a function of time (Fig.…”

Section: Light-induced Current and [Camp] I Change In The Physiologicmentioning

confidence: 99%

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Mechanism of Signal Amplification in the Olfactory Sensory Cilia

Takeuchi¹,

Kurahashi²

2005

J. Neurosci.

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Molecular mechanisms underlying olfactory signal amplification were investigated by monitoring cAMP dynamics in the intact sensory cilia. We saw that [cAMP] i increased superlinearly with time during odorant stimuli for Ͼ1 s. This time course was remarkably different from that obtained with the rapid quench method previously applied to the in vitro preparation, in which [cAMP] i change has been reported to be transient. The superlinear increase of [cAMP] i was attributable to a gradual increase of cAMP production rate that was consistent with the thermodynamical interaction model between elemental molecules, as has been revealed on the rod photoreceptor cell. It thus seems likely that the fundamental mechanism for molecular interactions between olfactory transduction elements is similar to that of the rod. In olfaction, however, cAMP production was extremely small (ϳ200,000 molecules/s/cell at the maximum), in contrast to the cGMP hydrolysis in the rod (250,000 molecules/photon). The observed numbers indicate that the olfactory receptor cell has lower amplification at the enzymatic cascade. Seemingly, such low amplification is a disadvantage for the signal transduction, but this unique mechanism would be essential to reduce the loss of ATP that is broadly used for the activities of cells. Apparently, transduction by a smaller number of second-messenger formations would be achieved by the fine ciliary structure that has a high surface-volume ratio. In addition, it is speculated that this low amplification at their enzymatic processes may be the reason why the olfactory receptor cell has acquired high amplification at the final stage of transduction channels, using Ca 2ϩ as a third messenger.

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Section: Resultsmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Light-induced Current and [Camp] I Change In The Physiologicmentioning

confidence: 99%

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Mechanism of Signal Amplification in the Olfactory Sensory Cilia

Takeuchi¹,

Kurahashi²

2005

J. Neurosci.

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“…Several other molecular mechanisms, including phosphorylation of olfactory receptors (35,36) and adenylyl cyclase (37)(38)(39), have been proposed to play a role in odor adaptation. By using combined molecular, cellular, and behavioral analyses of gene-targeted mice, we can now begin to evaluate the relative contribution of each of these mechanisms to odor perception.…”

Section: Discussionmentioning

confidence: 99%

Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice

Kelliher

Ziesmann

Munger

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Odor stimulation of olfactory sensory neurons (OSNs) leads to both the activation and subsequent desensitization of a heteromultimeric cyclic-nucleotide-gated (CNG) channel present in these cells. The native olfactory CNG channel consists of three distinct subunits: CNGA2, CNGA4, and CNGB1b. Mice in which the CNGA4 gene has been deleted display defective Ca 2؉ ͞calmodulin-dependent inhibition of the CNG channel, resulting in a striking reduction in adaptation of the odor-induced electrophysiological response in the OSNs. These mutants therefore afford an excellent opportunity to assess the importance of Ca 2؉ -mediated CNG channel desensitization for odor discrimination and adaptation in behaving animals. By using an operant conditioning paradigm, we show that CNGA4-null mice are profoundly impaired in the detection and discrimination of olfactory stimuli in the presence of an adapting background odor. The extent of this impairment depends on both the concentration and the molecular identity of the adapting stimulus. Thus, Ca 2؉ -dependent desensitization of the odor response in the OSNs mediated by the CNGA4 subunit is essential for normal odor sensation and adaptation of freely behaving mice, preventing saturation of the olfactory signal transduction machinery and extending the range of odor detection and discrimination.

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“…In this case, several aspects of the response to a subsequent stimulus are altered, including a decrease in the slope of the rising phase, as well as an increase in the speed of decay, of the stimulus-induced inward current (7,13). Experiments (15) have demonstrated that the molecular mechanisms responsible for desensitization are likely to act upstream of cAMP production; inhibition of adenylyl cyclase activity by CaMK is a possible mechanism (13). Longer-lasting adaptation effects with recovery time constants of minutes also have been reported (7).…”

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confidence: 99%

Computational model of the cAMP-mediated sensory response and calcium-dependent adaptation in vertebrate olfactory receptor neurons

Dougherty

Wright

Yew

2005

Proc. Natl. Acad. Sci. U.S.A.

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We develop a mechanistic mathematical model of the G-protein coupled signaling pathway responsible for generating current responses in frog olfactory receptor neurons. The model incorporates descriptions of ligand-receptor interaction, intracellular transduction events involving the second messenger cAMP, effector ion-channel activity, and calcium-mediated feedback steps. We parameterized the model with respect to suction pipette current recordings from single cells stimulated with multiple odor concentrations. The proposed model accurately predicts the receptorcurrent response of the neuron to brief and prolonged odorant exposure and is able to produce the adaptation observed under repeated or sustained stimulation.mathematical model ͉ receptor neuron ͉ olfaction ͉ signal transduction ͉ cilia S ensory transduction of odors occurs in olfactory receptor neurons (ORNs) located in the olfactory epithelium of vertebrates and the antennal structures of invertebrates (1). The first step in transduction is the binding of an odorant molecule to a seven-transmembrane-domain receptor protein in the cilia of an ORN. This interaction triggers a G-protein-coupled cascade that activates the enzyme adenylyl cyclase, resulting in an increase in intraciliary adenosine-3Ј,5Ј-cyclic monophosphate (cAMP). When cAMP increases, it opens cyclic nucleotidegated (CNG) channels, allowing calcium and other extracellular cations into the cilia and generating an inward current. Elevated Ca 2ϩ levels in the cilia activate Ca 2ϩ -gated chloride [Cl(Ca)] channels, creating an outward flow of Cl Ϫ ions and producing amplification of the inward current (2-4) that results in membrane depolarization and the generation of action potentials in the cell soma (5). This increase in intracellular calcium initiates termination and adaptation of the cell's response by means of deactivation and feedback mechanisms, including interactions mediated by Ca 2ϩ -calmodulin (CaCaM) and Ca 2ϩ ͞calmodulin-kinase II (CaMK) (6-10). The Cl(Ca) channels remain open until enough calcium is extruded from the cilia via the Na͞Ca exchanger (NCX) (11).After stimulation, an ORNЈs response to subsequent stimuli becomes attenuated. Short-term adaptation is observed as a decrease in responsiveness to odor presentations that occur within a few seconds after a brief stimulus (7); it may be mediated in part by CaCaM inhibition of the CNG channel (12). Desensitization occurs when an odor is experienced for a sustained interval of at least several seconds: the ORNЈs response declines while the stimulus continues to be present (13,14). In this case, several aspects of the response to a subsequent stimulus are altered, including a decrease in the slope of the rising phase, as well as an increase in the speed of decay, of the stimulus-induced inward current (7, 13). Experiments (15) have demonstrated that the molecular mechanisms responsible for desensitization are likely to act upstream of cAMP production; inhibition of adenylyl cyclase activity by CaMK is a possible mechanism (13). L...

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Photolysis of caged cyclic AMP in the ciliary cytoplasm of the newt olfactory receptor cell

Cited by 44 publications

References 37 publications

Mechanism of Signal Amplification in the Olfactory Sensory Cilia

Mechanism of Signal Amplification in the Olfactory Sensory Cilia

Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice

Computational model of the cAMP-mediated sensory response and calcium-dependent adaptation in vertebrate olfactory receptor neurons

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