scholarly journals Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye

2017 ◽  
Vol 117 (5) ◽  
pp. 1935-1947 ◽  
Author(s):  
Harumitsu Hirata ◽  
Kamila Mizerska ◽  
Valentina Dallacasagrande ◽  
Victor H. Guaiquil ◽  
Mark I. Rosenblatt
Keyword(s):  
Epithelial Cell ◽  
Sensory Information ◽  
Sensory Transduction ◽  
High Threshold ◽  
Nerve Terminals ◽  
Transduction Mechanisms ◽  
Cell Layers ◽  
Cold Sensitive ◽  
Low Threshold ◽  
Ganglion Neurons

It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing sensory information. We arrived at this conclusion by removing the epithelial cell layers of the cornea in which the nerve terminals reside but leaving the underlying stromal nerves undisturbed.

Benzolamide inhibits low-threshold calcium currents in hippocampal pyramidal neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2774-2777 ◽  
Author(s):  
J. A. Gottfried ◽  
M. Chesler
Keyword(s):  
Carbonic Anhydrase ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Ca Currents

1. Benzolamide is a poorly permeant sulfonamide inhibitor of the enzyme carbonic anhydrase. We studied the effect of benzolamide on low-threshold (LT) Ca currents in neonatal hippocampal CAl neurons. 2. In hippocampal slices, benzolamide (2-10 microM) inhibited the LT current 30-75% in voltage-clamped CAl pyramidal cells (n = 6). In slices bathed in N-2-hydroxypiperazine-N'-2-ethane-sulfonic acid (HEPES)-buffered Ringer, benzolamide also reduced the LT current, indicating that the action of the drug was not bicarbonate dependent. 3. Benzolamide inhibited LT Ca currents 20-75% in acutely dissociated CAl neurons in HEPES (n = 18): inhibition was 36 +/- 8% (mean +/- SE; n = 7) and 50 +/- 8% (n = 7) at 10 and 50 microM benzolamide, respectively. By contrast, high-threshold calcium currents recorded in CAl pyramidal cells (n = 18) and dorsal root ganglion neurons (n = 4) were virtually unaffected by benzolamide. 4. These results indicate that benzolamide inhibits LT Ca channels in central neurons and suggest caution in the use of this agent to inhibit extracellular carbonic anhydrase in excitable tissues.

scholarly journals Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca2+ Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons

2006 ◽  
Vol 129 (1) ◽  
pp. 57-77 ◽  
Author(s):  
Bertrand Coste ◽  
Marcel Crest ◽  
Patrick Delmas
Keyword(s):  
Hair Cells ◽  
Low Voltage ◽  
Sensory Information ◽  
Cell Types ◽  
High Threshold ◽  
Type I ◽  
Mechanosensitive Channels ◽  
Drg Neurons ◽  
Pathological Pain ◽  
Low Threshold

Low voltage–activated (LVA) T-type Ca2+ (ICaT) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remain poorly understood. Here, we carried out a detailed characterization of LVA currents in DRG neurons by using a method for better separation of NaN/Nav1.9 and ICaT currents. NaN/Nav1.9 was inhibited by inorganic ICa blockers as follows (IC50, μM): La3+ (46) &gt; Cd2+ (233) &gt; Ni2+ (892) and by mibefradil, a non-dihydropyridine ICaT antagonist. Amiloride, however, a preferential Cav3.2 channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni2+-resistant ICaT (AR-ICaT) contribute differentially to LVA currents in distinct sensory cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-Aδ–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aα/β cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR-ICaT was restricted to CII-nociceptors, putative D-hair cells, and Aα/β-like cells. These cell types distinguished by their current-signature displayed different types of mechanosensitive channels. CI- and CII-nociceptors displayed amiloride-sensitive high-threshold mechanical currents with slow or no adaptation, respectively. Putative D-hair and Aα/β-like cells had low-threshold mechanical currents, which were distinguished by their adapting kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express specific combinations of LVA and mechanosensitive channels, which are likely to play a key role in shaping responses of DRG neurons transmitting different sensory modalities.

Responses of intact and injured sural nerve fibers to cooling and menthol

2014 ◽  
Vol 111 (10) ◽  
pp. 2071-2083 ◽  
Author(s):  
Alina Teliban ◽  
Fabian Bartsch ◽  
Marek Struck ◽  
Ralf Baron ◽  
Wilfrid Jänig
Keyword(s):  
Sural Nerve ◽  
Nerve Fibers ◽  
Afferent Nerve ◽  
High Threshold ◽  
C Fibers ◽  
Afferent Nerve Fibers ◽  
Cold Sensitive ◽  
Low Threshold

Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6–12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact ( n = 12) and 90% of injured ( n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers ( n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers ( n = 25) and almost no A-fibers ( n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.

Agonists for neuropeptide Y receptor subtypes NPY-1 and NPY-2 have opposite actions on rat nodose neuron calcium currents

1993 ◽  
Vol 70 (1) ◽  
pp. 324-330 ◽  
Author(s):  
J. W. Wiley ◽  
R. A. Gross ◽  
R. L. MacDonald
Keyword(s):  
Neuropeptide Y ◽  
Calcium Current ◽  
Calcium Currents ◽  
Peak Amplitude ◽  
High Threshold ◽  
Receptor Subtypes ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Ganglion Neurons

1. The whole-cell variation of the patch-clamp technique was used to study the effect of neuropeptide Y (NPY) and preferential agonists for the NPY-1 and NPY-2 receptor subtypes on voltage-dependent calcium currents in acutely dissociated postnatal rat nodose ganglion neurons. 2. Both low- and high-threshold calcium current components were present. NPY altered voltage-dependent calcium currents in approximately 50% of neurons studied. NPY (0.1-100 nM, ED50 6 nM) decreased the peak amplitude of transient high-threshold calcium currents in approximately 45% of the neurons. NPY (100 nM) decreased the peak amplitude of these currents 31 +/- 5% (mean +/- SE). However, in approximately 5% of the neurons NPY (100 nM) caused a reversible and reproducible increase in transient high-threshold calcium currents of 21 +/- 4%. NPY did not affect either transient low-threshold or slowly inactivating high-threshold calcium current components. 3. Application of the C-terminal fragment NPY 13-36 (100 nM), a preferential agonist for NPY-2 receptors, reversibly decreased the peak amplitude of transient high-threshold calcium currents by 26 +/- 5% in 9 of 20 cells (45%). Application of [Pro34]-NPY (100 nM), a preferential agonist for NPY-1 receptors, reversibly increased the peak amplitude of transient high-threshold calcium currents 20 +/- 4% in 23 out of 48 neurons (48%). Six of 20 neurons (30%) responded to application of both agonists. Neither the NPY-1 nor NPY-2 agonists affected transient low-threshold or slowly inactivating high-threshold calcium current components.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Low-Threshold, Persistent Sodium Current in Rat Large Dorsal Root Ganglion Neurons in Culture

1997 ◽  
Vol 77 (3) ◽  
pp. 1503-1513 ◽  
Author(s):  
Mark D. Baker ◽  
Hugh Bostock
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Sodium Current ◽  
Threshold Current ◽  
Persistent Current ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Large Neurons

Baker, Mark D. and Hugh Bostock. Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture. J. Neurophysiol. 77: 1503–1513, 1997. Dorsal root ganglion neurons from adult rats (≥200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50–75 μm apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to −35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to −70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least −70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.

TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

2003 ◽  
Vol 90 (1) ◽  
pp. 515-520 ◽  
Author(s):  
Michele L. Nealen ◽  
Michael S. Gold ◽  
Paul D. Thut ◽  
Michael J. Caterina
Keyword(s):  
Cold Temperatures ◽  
Trigeminal Neurons ◽  
Cold Receptors ◽  
Electrophysiological Studies ◽  
Ionic Mechanisms ◽  
Cold Sensitive ◽  
Low Threshold ◽  
Ion Channel Proteins ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons

Recent electrophysiological studies of cultured dorsal root and trigeminal ganglion neurons have suggested that multiple ionic mechanisms underlie the peripheral detection of cold temperatures. Several candidate “cold receptors,” all of them ion channel proteins, have been implicated in this process. One of the most promising candidates is TRPM8, a nonselective cationic channel expressed in a subpopulation of sensory neurons that is activated both by decreases in temperature and the cooling compound menthol. However, evidence for the expression of TRPM8 in functionally defined cold-sensitive neurons has been lacking. Here, we combine fluorometric calcium imaging of cultured rat trigeminal neurons with single-cell RT-PCR to demonstrate that there are distinct subpopulations of cold responsive neurons and that TRPM8 likely contributes to cold transduction in one of them. TRPM8 is preferentially expressed within a subset of rapidly responsive, low-threshold (approximately 30°C), cold-sensitive neurons. A distinct class of slowly responsive cold-sensitive neurons that is activated at lower temperatures (approximately 20°C) generally lacks detectable TRPM8 mRNA. Together with previous findings, our data support the notion that cold responsive neurons are functionally heterogeneous.

scholarly journals Heterogeneous Potassium Conductances Contribute to the Diverse Firing Properties of Postnatal Mouse Vestibular Ganglion Neurons

2006 ◽  
Vol 96 (5) ◽  
pp. 2364-2376 ◽  
Author(s):  
Jessica R. Risner ◽  
Jeffrey R. Holt
Keyword(s):  
Action Potential ◽  
Tuning Curve ◽  
Sine Wave ◽  
High Threshold ◽  
Whole Cell ◽  
Vestibular Ganglion ◽  
Potassium Conductances ◽  
Low Threshold ◽  
Firing Properties ◽  
Ganglion Neurons

How mechanical information is encoded in the vestibular periphery has not been clarified. To begin to address the issue we examined the intrinsic firing properties of postnatal mouse vestibular ganglion neurons using the whole cell, tight-seal technique in current-clamp mode. We categorized two populations of neurons based on the threshold required to evoke an action potential. Low-threshold neurons fired with an average minimum current injection of −43 pA, whereas high-threshold neurons required −176 pA. Using sine-wave stimuli, we found that the neurons were inherently tuned with best frequencies that ranged up to 40 Hz. To investigate the membrane properties that contributed to the variability in firing properties we examined the same neurons in voltage-clamp mode. High-threshold neurons had larger cell bodies and whole cell capacitances but a resting conductance density of 0.18 nS/pF, nearly identical to that of low-threshold neurons, suggesting that cell size was an important parameter determining threshold. We also found that vestibular ganglion neurons expressed a heterogeneous population of potassium conductances. TEA-sensitive conductances contributed to the position of the tuning curve in the frequency domain. A 4-AP–sensitive conductance was active at rest and hyperpolarized resting potential, limited spontaneous activity, raised threshold, and prevented repetitive firing. In response to sine-wave stimulation 4-AP–sensitive conductances prevented action potential generation at low frequencies and thus contributed to the high-pass corner of the tuning curve. The mean low-pass corner (about 29 Hz) was determined by the membrane time constant. Together these factors contributed to the sharply tuned, band-pass characteristics intrinsic to postnatal vestibular ganglion neurons.

scholarly journals Odontoblast TRPC5 channels signal cold pain in teeth

2021 ◽  
Vol 7 (13) ◽  
pp. eabf5567
Author(s):  
Laura Bernal ◽  
Pamela Sotelo-Hitschfeld ◽  
Christine König ◽  
Viktor Sinica ◽  
Amanda Wyatt ◽  
...  
Keyword(s):  
Relative Sensitivity ◽  
Cellular Component ◽  
Sensory Transduction ◽  
Cold Sensation ◽  
Cold Pain ◽  
Sensing System ◽  
Cold Sensitive ◽  
Cellular Components ◽  
Cold Sensor ◽  
Cold Sensing

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5’s relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system.

Chronic Estrogen Sensitizes a Subset of Mechanosensitive Afferents Innervating the Uterine Cervix

2005 ◽  
Vol 93 (4) ◽  
pp. 2167-2173 ◽  
Author(s):  
Baogang Liu ◽  
James C. Eisenach ◽  
Chuanyao Tong
Keyword(s):  
Spontaneous Activity ◽  
Uterine Cervix ◽  
Firing Frequency ◽  
High Threshold ◽  
Group 13 ◽  
Ovx Rats ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Group 5 ◽  
Afferent Response

Estrogen increases reflex nocifensive responses to distension of the uterus and the urinary bladder, but estrogen's effects on afferent response to distension of the uterine cervix, the site of obstetric and some gynecologic pain, has not been studied. Here, single fiber recording of hypogastric nerve responses to uterine cervical distension were obtained from ovariectomized (OVX) rats and OVX rats treated with estrogen (ES). Spontaneous activity was greater in the ES group (13 of 24 units; 54%) than in the OVX group (6 of 27 units; 22%). ES differentially altered the response of low- and high-threshold units to distension. For high-threshold units, firing frequency was increased two- to fourfold with 60–100 gm distension in ES compared with OVX groups ( P < 0.05). In contrast, the response of low-threshold units to distension was not altered by ES. About one-half of units tested in each group responded to a temperature increase from 35 to 49°C. A greater proportion of thermosensitive units were also mechanosensitive in the ES group (7 of 8 afferents, 88%) than in the OVX group (5 of 11 afferents, 45%). Acute application of ES in OVX rats failed to evoke or increase distension-induced responses. These data show the polymodal nature of afferent fibers innervating the uterine cervix. Increased spontaneous activity with ES may play a part in remodeling of the cervical tissue, whereas selective sensitization of high-threshold units by ES might underlie increased pain responses to cervical distension. Failure of acute ES treatment to mimic this suggests a genomic effect.

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