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) > Cd2+ (233) > 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.

Effects of KCNQ channel blockers on K+ currents in vestibular hair cells

2001 ◽  
Vol 280 (3) ◽  
pp. C473-C480 ◽  
Author(s):  
Katherine J. Rennie ◽  
Tianxiang Weng ◽  
Manning J. Correia
Keyword(s):  
Steady State ◽  
Hair Cells ◽  
Low Voltage ◽  
Dissociation Constants ◽  
Channel Blockers ◽  
Type I ◽  
Type Ii ◽  
Kcnq Channels ◽  
Vestibular Hair Cells ◽  
Inward Currents

Linopirdine and XE991, selective blockers of K+ channels belonging to the KCNQ family, were applied to hair cells isolated from gerbil vestibular system and to hair cells in slices of pigeon crista. In type II hair cells, both compounds inhibited a slowly activating, slowly inactivating component of the macroscopic current recruited at potentials above −60 mV. The dissociation constants for linopirdine and XE991 block were <5 μM. A similar component of the current was also blocked by 50 μM capsaicin in gerbil type II hair cells. All three drugs blocked a current component that showed steady-state inactivation and a biexponential inactivation with time constants of ∼300 ms and 4 s. Linopirdine (10 μM) reduced inward currents through the low-voltage-activated K+ current in type I hair cells, but concentrations up to 200 μM had little effect on steady-state outward K+ current in these cells. These results suggest that KCNQ channels may be present in amniote vestibular hair cells.

Vestibular Type I and Type II Hair Cells. 1: Morphometric Identification in the Pigeon and Gerbil

1997 ◽  
Vol 7 (5) ◽  
pp. 393-406
Author(s):  
Anthony J. Ricci ◽  
Katherine J. Rennie ◽  
Stephen L. Cochran ◽  
Golda A. Kevetter ◽  
Manning J. Correia
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Body Width ◽  
Fixed Tissue ◽  
Neck Width ◽  
I Cells ◽  
Plate Width

Classically, type I and type II vestibular hair cells have been defined by their afferent innervation patterns. Little quantitative information exists on the intrinsic morphometric differences between hair cell types. Data presented here define a quantitative method for distinguishing hair cell types based on the morphometric properties of the hair cell’s neck region. The method is based initially on fixed histological sections, where hair cell types were identified by innervation pattern, type I cells having an afferent calyx. Cells were viewed using light microscopy, images were digitized, and measurements were made of the cell body width, the cuticular plate width, and the neck width. A plot of the ratio of the neck width to cuticular plate width (NPR) versus the ratio of the neck width to the body width (NBR) established four quadrants based on the best separation of type I and type II hair cells. The combination of the two variables made the accuracy of predicting either type I or type II hair cells greater than 90%. Statistical cluster analysis confirmed the quadrant separation. Similar analysis was performed on dissociated hair cells from semicircular canal, utricle, and lagena, giving results statistically similar to those of the fixed tissue. Additional comparisons were made between fixed tissue and isolated hair cells as well as across species (pigeon and gerbil) and between end organs (semicircular canal, utricle, and lagena). In each case, the same morphometric boundaries could be used to establish four quadrants, where quadrant 1 was predominantly type I cells and quadrant 3 was almost exclusively type II hair cells. The quadrant separations were confirmed statistically by cluster analysis. These data demonstrate that there are intrinsic morphometric differences between type I and type II hair cells and that these differences can be maintained when the hair cells are dissociated from their respective epithelia.

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.

Autocorrelation Analysis of Hair Bundle Structure in the Utricle

2006 ◽  
Vol 96 (5) ◽  
pp. 2653-2669 ◽  
Author(s):  
M. H. Rowe ◽  
E. H. Peterson
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Cell Types ◽  
Head Movements ◽  
Type I ◽  
Autocorrelation Analysis ◽  
Response Dynamics ◽  
Hair Bundles ◽  
Vestibular Organs ◽  
Bundle Structure

The ability of hair bundles to signal head movements and sounds depends significantly on their structure, but a quantitative picture of bundle structure has proved elusive. The problem is acute for vestibular organs because their hair bundles exhibit complex morphologies that vary with endorgan, hair cell type, and epithelial locus. Here we use autocorrelation analysis to quantify stereociliary arrays (the number, spacing, and distribution of stereocilia) on hair cells of the turtle utricle. Our first goal was to characterize zonal variation across the macula, from medial extrastriola, through striola, to lateral extrastriola. This is important because it may help explain zonal variation in response dynamics of utricular hair cells and afferents. We also use known differences in type I and II bundles to estimate array characteristics of these two hair cell types. Our second goal was to quantify variation in array orientation at single macular loci and use this to estimate directional tuning in utricular afferents. Our major findings are that, of the features measured, array width is the most distinctive feature of striolar bundles, and within the striola there are significant, negatively correlated gradients in stereocilia number and spacing that parallel gradients in bundle heights. Together with previous results on stereocilia number and bundle heights, our results support the hypothesis that striolar hair cells are specialized to signal high-frequency/acceleration head movements. Finally, there is substantial variation in bundle orientation at single macular loci that may help explain why utricular afferents respond to stimuli orthogonal to their preferred directions.

scholarly journals Immunohistochemical localization of vimentin in the gerbil inner ear.

1989 ◽  
Vol 37 (12) ◽  
pp. 1787-1797 ◽  
Author(s):  
B A Schulte ◽  
J C Adams
Keyword(s):  
Epithelial Cells ◽  
Inner Ear ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Cell Types ◽  
Immunohistochemical Localization ◽  
Outer Hair Cells ◽  
Type I ◽  
Basal Cells

Cells containing immunoreactive vimentin-type intermediate filaments (IF) were identified in paraffin sections and whole-mount preparations of the gerbil inner ear. Most connective tissue cells showed positive immunostaining, although one unusual class of stromal cell lacked vimentin. Several different types of epithelial cells contained high levels of vimentin. In the cochlea, Deiters' cells, inner phalangeal cells, Boettcher's cells, some outer sulcus cells, and the intermediate cells of the stria vascularis showed strong immunoreactivity. Strial basal cells exhibited weaker and less consistent staining. Neither inner nor outer hair cells were stained. In the vestibular system, hair cells with a morphology and location more characteristic of type I than of type II cells showed strong immunostaining for vimentin. Supporting cells in vestibular neurosensory epithelium stained with less intensity. These results were surprising because epithelial cells in vivo only rarely express vimentin-type IF. Although the functional significance of vimentin remains to be established, its presence in some but not other highly specialized cell types provides an excellent marker for investigating the lineage and morphogenesis of the complex inner ear tissues.

scholarly journals A Biophysical Model of Nonquantal Transmission at the Vestibular Hair Cell-Calyx Synapse: KLV currents Modulate Fast Electrical and Slow K+ potentials in the Synaptic Cleft

2021 ◽  
Author(s):  
Aravind Chenrayan Govindaraju ◽  
Imran H Quraishi ◽  
Anna Lysakowski ◽  
Ruth Anne Eatock ◽  
Robert M Raphael
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Low Voltage ◽  
Electrical Potential ◽  
Synaptic Cleft ◽  
Biophysical Model ◽  
Afferent Neuron ◽  
Type I ◽  
Significant Finding ◽  
Vestibular Hair Cells

Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal referred to as a calyx. The vestibular hair cell-calyx synapse supports nonquantal transmission (NQT), a neurotransmitter-independent mechanism that is exceptionally fast. The underlying biophysical mechanisms that give rise to NQT are not fully understood. Here we present a computational model of NQT that integrates morphological and electrophysiological data. The model predicts that NQT involves two processes: changes in cleft K+ concentration, as previously recognized, and very fast changes in cleft electrical potential. A significant finding is that changes in cleft electrical potential are faster than changes in [K+] or quantal transmission. The electrical potential mechanism thus provides a basis for the exceptional speed of neurotransmission between type I hair cells and primary neurons and explains experimental observations of fast postsynaptic currents. The [K+] mechanism increases the gain of NQT. Both processes are mediated by current flow through low-voltage-activated K+ (KLV) channels located in both pre-synaptic (hair cell) and post-synaptic (calyx inner face) membranes. The model further demonstrates that the calyx morphology is necessary for NQT; as calyx height is increased, NQT increases in size, speed and efficacy at depolarizing the afferent neuron. We propose that the calyx evolved to enhance NQT and speed up signals that drive vestibular reflexes essential for stabilizing the eyes and neck and maintaining balance during rapid and complex head motions.

Modulation of calcium currents by electrical activity

1996 ◽  
Vol 76 (4) ◽  
pp. 2595-2607 ◽  
Author(s):  
M. Li ◽  
M. Jia ◽  
R. D. Fields ◽  
P. G. Nelson
Keyword(s):  
Electrical Activity ◽  
Threshold Voltage ◽  
Time Course ◽  
Average Frequency ◽  
Calcium Currents ◽  
High Threshold ◽  
Drg Neurons ◽  
Mouse Dorsal Root Ganglion ◽  
Low Threshold ◽  
Tonic Stimulation

Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures for 1-2 days produced a downregulation of voltage sensitive calcium currents, which persisted for > or = 24 h after stimulation was terminated. This regulation varied with different patterns of activation. Both the magnitude and time course of regulation of the low-threshold voltage-activated (LVA) and high-threshold voltage-activated (HVA) currents were differentially sensitive to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation (10 Hz for 0.5 s every 2 s) with an average frequency of 2.5 Hz produced significantly more downregulation of HVA currents than did the tonic 2.5-Hz stimulation. The efficacy of phasic stimulation varied inversely with the interval between bursts. Thus phasic stimulation of 10 Hz for 0.5 s but delivered every 4 s produced no effects on HVA currents. Stimulation optimal for downregulation of Ca2+ currents also produced a decreased binding by the DRG neurons of an L-type Ca2+ channel antagonist. This suggests a downregulation by electrical activity of the number of Ca2+ channels, rather than an alteration in a constant number of channels. Depression of LVA currents was produced by all stimulus patterns tested, including 0.5-Hz tonic stimulation. Chronic stimulation with a stimulation pattern that downregulated Ca2+ currents also produced a slowing of the increase in intracellular Ca2+ (as measured by Fura-2/AM) that is produced acutely by repetitive stimulation. This is consonant with earlier studies of intracellular Ca2+ concentration kinetics in growth cones.

Myelinated Mechanically Insensitive Afferents From Monkey Hairy Skin: Heat-Response Properties

1998 ◽  
Vol 80 (3) ◽  
pp. 1082-1093 ◽  
Author(s):  
Rolf-Detlef Treede ◽  
Richard A. Meyer ◽  
James N. Campbell
Keyword(s):  
High Threshold ◽  
Type I ◽  
Type Ii ◽  
Pain Sensation ◽  
Search Technique ◽  
Hairy Skin ◽  
Heat Response ◽  
Low Threshold ◽  
First Pain ◽  
Aβ Fibers

Treede, Rolf-Detlef, Richard A. Meyer, and James N. Campbell. Myelinated mechanically insensitive afferents from monkey hairy skin: heat-response properties. J. Neurophysiol. 80: 1082–1093, 1998. To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 Aβ-fibers, 79 Aδ-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors ( n = 91) or low-threshold cold receptors ( n = 11). Nine Aβ-fibers and 41 Aδ-fibers were cutaneous nociceptors, and four Aδ-fibers innervated subcutaneous tissue. The majority of cutaneous A-fiber nociceptors were heat sensitive (43/50 = 86%). Heat-insensitive cutaneous A-fiber nociceptors consisted of one cold nociceptor, three silent nociceptors, and three high-threshold mechanoreceptors. Two types of response were observed to an intense heat stimulus (53°C, 30 s). Type I ( n = 26) was characterized by a long latency (mean: 5 s) and a late peak discharge (16 s). Type II ( n = 17) was characterized by a short latency (0.2 s) and an early peak discharge (0.5 s). Type I fibers exhibited faster conduction velocities (25 vs. 14 m/s) and higher heat thresholds (>53 vs. 47°C, 1-s duration) than type II fibers. The possibility that the type I heat response was a result of sensitization was tested in three fibers by determining the heat threshold to 30-s duration stimuli (42–46°C). For this long stimulus duration heat thresholds were reproducible across multiple runs, and the threshold to the 1-s duration stimulus was not altered by these tests. Thus fibers with a type I heat response were not high-threshold mechanoreceptors that developed a heat response through sensitization. Fibers with a type II heat response had significantly higher mechanical thresholds (median: 15 bar) than fibers with a type I heat response (5 bar). This finding accounts for the observation that type II heat responses were infrequently observed in earlier studies wherein the search technique depended on mechanical responsiveness. Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.

scholarly journals Development of K+ and Na+ conductances in rodent postnatal semicircular canal type I hair cells

2010 ◽  
Vol 298 (2) ◽  
pp. R351-R358 ◽  
Author(s):  
Gang Q. Li ◽  
Frances L. Meredith ◽  
Katherine J. Rennie
Keyword(s):  
Hair Cells ◽  
Low Voltage ◽  
Semicircular Canals ◽  
Input Resistance ◽  
Membrane Properties ◽  
Delayed Rectifier ◽  
Type I ◽  
Adult Type ◽  
Whole Cell Patch Clamp ◽  
Ionic Changes

The rodent vestibular system is immature at birth. During the first postnatal week, vestibular type I and type II hair cells start to acquire their characteristic morphology and afferent innervation. We have studied postnatal changes in the membrane properties of type I hair cells acutely isolated from the semicircular canals (SCC) of gerbils and rats using whole cell patch clamp and report for the first time developmental changes in ionic conductances in these cells. At postnatal day (P) 5 immature hair cells expressed a delayed rectifier K+ conductance ( GDR) which activated at potentials above approximately −50 mV in both species. Hair cells also expressed a transient Na+ conductance ( GNa) with a mean half-inactivation of approximately −90 mV. At P6 in rat and P7 in gerbil, a low-voltage activated K+ conductance ( GK,L) was first observed and conferred a low-input resistance, typical of adult type I hair cells, on SCC type I hair cells. GK,L expression in hair cells increased markedly during the second postnatal week and was present in all rat type I hair cells by P14. In gerbil hair cells, GK,L appeared later and was present in all type I hair cells by P19. During the third postnatal week, GNa expression declined and was absent by the fourth postnatal week in rat and the sixth postnatal week in gerbils. Understanding the ionic changes associated with hair cell maturation could help elucidate development and regeneration mechanisms in the inner ear.

Membrane currents of identified isolated rat corticotropes and gonadotropes

1987 ◽  
Vol 252 (3) ◽  
pp. E340-E346 ◽  
Author(s):  
C. Marchetti ◽  
G. V. Childs ◽  
A. M. Brown
Keyword(s):  
Anterior Pituitary ◽  
Cell Types ◽  
Membrane Currents ◽  
Calcium Currents ◽  
High Threshold ◽  
Releasing Hormone ◽  
Electrophysiological Recordings ◽  
Living State ◽  
Inward Currents ◽  
Low Threshold

Membrane currents of identified, isolated corticotropes and gonadotropes from mammalian anterior pituitary gland have been evaluated. Pituitary gonadotropes and corticotropes were isolated enzymatically and stained in the living state using biotinylated gonadotropin-releasing hormone (Bio-GnRH) or biotinylated corticotropin-releasing hormone (Bio-CRF) followed by avidin fluorescein. Electrophysiological recordings were made with patch-clamp electrodes in the whole-cell clamp configuration. Tetrodotoxin (TTX)-sensitive sodium currents were larger in corticotropes than in gonadotropes. Corticotropes showed two components of calcium currents, a transient low-threshold component and a longer lasting high-threshold component. Small TTX-resistant inward currents were present also in gonadotropes, and both cell types had transient and steady potassium currents.

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