Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy.
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Sensitivity to the pungent vanilloid, capsaicin, defines a subpopulation of primary sensory neurons that are mainly polymodal nociceptors. The recently cloned vanilloid receptor subtype 1 (VR1) is activated by capsaicin and noxious heat. Using combined in situ hybridization and histochemical methods, we have characterized in sensory ganglia the expression of VR1 mRNA. We show that this receptor is almost exclusively expressed by neurofilament-negative small- and medium-sized dorsal root ganglion cells. Within this population, VR1 mRNA is detected at widely varying levels in both the NGF receptor (trkA)-positive, peptide-producing cells that elicit neurogenic inflammation and the functionally less characterized glial cell line-derived neurotrophic factor-responsive cells that bind lectin Griffonia simplicifolia isolectin B4 (IB4). Cells without detectable levels of VR1 mRNA are found in both classes. A subpopulation of the IB4-binding cells that produce somatostatin has relatively low levels of VR1 mRNA. A previously uncharacterized population of very small cells that express the receptor tyrosine kinase (RET) and that do not label for trkA or IB4-binding has the highest relative levels of VR1 mRNA. The majority of small visceral sensory neurons of the nodose ganglion also express VR1 mRNA, in conjunction with the BDNF receptor trkB but not trkA. Axotomy results in the downregulation of VR1 mRNA in dorsal root ganglion cells. Our data emphasize the heterogeneity of VR1 mRNA expression by subclasses of small sensory neurons, and this may result in their differential sensitivity to chemical and noxious heat stimuli. Our results also indicate that peripherally derived trophic factors may regulate levels of VR1 mRNA. (+info)
Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea.
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In vitro electrophysiological techniques were used to examine the effect of bradykinin on guinea pig trachea and bronchus afferent nerve endings arising from the nodose or jugular ganglia. The data reveal that bradykinin activates nerve terminals of jugular C and Adelta fibers. Although the fibers were too few in number to study rigorously, bradykinin also stimulated nodose C fibers innervating the trachea and bronchus. In contrast, Adelta fibers arising from the nodose ganglion were unresponsive to bradykinin challenge. The responses in both jugular C and Adelta fiber types were blocked by a selective bradykinin B2 receptor antagonist and were not dependent on the efferent release of sensory neuropeptides. These data indicate that the sensitivity of guinea pig airway afferent fibers to bradykinin is dependent more on the ganglionic origin of the cell body than on the conduction velocity of its axon. (+info)
Calcium regulation of a slow post-spike hyperpolarization in vagal afferent neurons.
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Activation of distinct classes of potassium channels can dramatically affect the frequency and the pattern of neuronal firing. In a subpopulation of vagal afferent neurons (nodose ganglion neurons), the pattern of impulse activity is effectively modulated by a Ca2+-dependent K+ current. This current produces a post-spike hyperpolarization (AHPslow) that plays a critical role in the regulation of membrane excitability and is responsible for spike-frequency accommodation in these neurons. Inhibition of the AHPslow by a number of endogenous autacoids (e.g., histamine, serotonin, prostanoids, and bradykinin) results in an increase in the firing frequency of vagal afferent neurons from <0.1 to >10 Hz. After a single action potential, the AHPslow in nodose neurons displays a slow rise time to peak (0.3-0.5 s) and a long duration (3-15 s). The slow kinetics of the AHPslow are due, in part, to Ca2+ discharge from an intracellular Ca2+-induced Ca2+ release (CICR) pool. Action potential-evoked Ca2+ influx via either L or N type Ca2+ channels triggers CICR. Surprisingly, although L type channels generate 60% of action potential-induced CICR, only Ca2+ influx through N type Ca2+ channels can trigger the CICR-dependent AHPslow. These observations suggest that a close physical proximity exists between endoplasmic reticulum ryanodine receptors and plasma membrane N type Ca2+ channels and AHPslow potassium channels. Such an anatomical relation might be particularly beneficial for modulation of spike-frequency adaptation in vagal afferent neurons. (+info)
Opioid modulation of calcium current in cultured sensory neurons: mu-modulation of baroreceptor input.
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We used the whole cell open-patch or perforated-patch technique to characterize mu-opioid modulation of Ca(2+) current (I(Ca)) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The mu-opiate receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I(Ca) in 95% of neonatal [postnatal day (P)1-P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20-P35) and 61% of adult cells (P60-P110) responded to DAGO. DAGO-mediated inhibition of I(Ca) was naloxone sensitive, irreversible in the presence of guanosine 5'-O-(3-thiotriphosphate), absent with guanosine 5'-O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO's inhibition of I(Ca) was G protein mediated. Incubation of neurons with omega-conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of omega-conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC(50) of 1.82 x 10(-8) M. DAGO slowed activation of I(Ca), but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, mu-opiate modulation of I(Ca) in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of mu-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii. (+info)
Adaptation of guinea-pig vagal airway afferent neurones to mechanical stimulation.
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1. Intracellular and extracellular electrophysiological recording techniques were employed to examine the mechanisms involved in adaptation of guinea-pig airway sensory neurones to suprathreshold mechanical stimulation in vitro. Extracellular recordings performed using an in vitro airway preparation revealed two unambiguously distinct subsets of mechanically sensitive nerve endings in the trachea/bronchus. In one group of fibres, the mechanical stimulus caused a brief burst of action potentials, after which the nerve rapidly adapted. In the other group of fibres, repetitive action potentials were evoked as long as the stimulus was maintained above threshold. 2. The adaptation response strictly correlated with ganglionic origin of the soma. Those fibres derived from the nodose ganglion adapted rapidly, whereas those derived from the jugular ganglion were slowly or non-adapting. 3. Intracellular recordings from airway-identified neurones in isolated intact ganglia revealed that the majority of neurones within either the nodose or jugular ganglion adapted rapidly to prolonged suprathreshold depolarizing current injections. 4. The electrophysiological adaptation of nodose ganglion-derived neurones following prolonged suprathreshold current steps was greatly reduced by 4-aminopyridine. However, 4-aminopyridine did not affect the adaptation of rapidly adapting nodose ganglion-derived nerve endings in response to mechanical stimuli. 5. The data suggest that ganglionic origin dictates adaptive characteristics of guinea-pig tracheal and mainstem bronchial afferent neurones in response to mechanical stimulation. Also, the rapid adaptation of nodose nerve endings in the trachea observed during a mechanical stimulus does not appear to be related to the adaptation observed at the soma during prolonged suprathreshold depolarizing current injections. (+info)
Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons.
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Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and interleukin 6 (IL-6) comprise a group of structurally related cytokines that promote the survival of subsets of neurons in the developing peripheral nervous system, but the signaling pathways activated by these cytokines that prevent neuronal apoptosis are unclear. Here, we show that these cytokines activate NF-kappaB in cytokine-dependent developing sensory neurons. Preventing NF-kappaB activation with a super-repressor IkappaB-alpha protein markedly reduces the number of neurons that survive in the presence of cytokines, but has no effect on the survival response of the same neurons to brain-derived neurotrophic factors (BDNF), an unrelated neurotrophic factor that binds to a different class of receptors. Cytokine-dependent sensory neurons cultured from embryos that lack p65, a transcriptionally active subunit of NF-kappaB, have a markedly impaired ability to survive in response to cytokines, but respond normally to BDNF. There is increased apoptosis of cytokine- dependent neurons in p65(-/)- embryos in vivo, resulting in a reduction in the total number of these neurons compared with their numbers in wild-type embryos. These results demonstrate that NF-kappaB plays a key role in mediating the survival response of developing neurons to cytokines. (+info)
Establishing neuronal identity in vertebrate neurogenic placodes.
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The trigeminal and epibranchial placodes of vertebrate embryos form different types of sensory neurons. The trigeminal placodes form cutaneous sensory neurons that innervate the face and jaws, while the epibranchial placodes (geniculate, petrosal and nodose) form visceral sensory neurons that innervate taste buds and visceral organs. In the chick embryo, the ophthalmic trigeminal (opV) placode expresses the paired homeodomain transcription factor Pax3 from very early stages, while the epibranchial placodes express Pax2. Here, we show that Pax3 expression in explanted opV placode ectoderm correlates at the single cell level with neuronal specification and with commitment to an opV fate. When opV (trigeminal) ectoderm is grafted in place of the nodose (epibranchial) placode, Pax3-expressing cells form Pax3-positive neurons on the same schedule as in the opV placode. In contrast, Pax3-negative cells in the grafted ectoderm are induced to express the epibranchial placode marker Pax2 and form neurons in the nodose ganglion that express the epibranchial neuron marker Phox2a on the same schedule as host nodose neurons. They also project neurites along central and peripheral nodose neurite pathways and survive until well after the main period of cell death in the nodose ganglion. The older the opV ectoderm is at the time of grafting, the more Pax3-positive cells it contains and the more committed it is to an opV fate. Our results suggest that, within the neurogenic placodes, there does not appear to be a two-step induction of 'generic' neurons followed by specification of the neuron to a particular fate. Instead, there seems to be a one-step induction in which neuronal subtype identity is coupled to neuronal differentiation. (+info)
Sexually dimorphic regulation of NK-1 receptor-mediated electrophysiological responses in vagal primary afferent neurons.
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Neurons can display sexual dimorphism in receptor expression, neurotransmitter release, and synaptic plasticity. We have detected sexual dimorphism in functional tachykinin receptors in vagal afferents (nodose ganglion neurons, NGNs) by studying the effects of hormonal variation on the depolarizing actions of substance P (SP) in female guinea pig NGNs. Using conventional "sharp" microelectrode recording plus measurement of serum 17beta-estradiol values, we examined SP responses in NGNs isolated from 1) ovariectomized females (OVX), 2) OVX females treated with 17beta-estradiol (OVX + E2), 3) pregnant females, and 4) males. Depending on various manipulations, 19-41% female NGNs were depolarized (16 +/- 1.1 mV, mean +/- SE) by 100 nM SP acting through NK-1 receptors. The NGNs of OVX + E2 females (41%, 15/37; 17 +/- 2.1 mV) and pregnant females (41%, 32/79; 16 +/- 1.7 mV) were more likely to respond to SP than those of control males (P < 0.001). The percentage of SP-sensitive NGNs from OVX females (19%, 21/109; 15 +/- 1.9 mV) was not significantly different (P = 0.361) from that of control males (13%, 11/83; 13 +/- 2.0 mV). The serum 17beta-estradiol values for OVX + E2, pregnant, and OVX females were 23.9 +/- 3.3 pg/ml (n = 8), 16.0 +/- 2.4 pg/ml (n = 4), and 3.9 +/- 0.3 pg/ml (n = 8), respectively. These data indicate that there is a gender difference in NK-1 receptor expression in guinea pig nodose neurons, and they suggest that estrogen may modulate SP responsiveness in these neurons. (+info)