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PubMed2005

Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat.

The lumen of the inner ear has an unusually low concentration of endolymphatic Na+, which is important for transduction processes. We have recently shown that glucocorticoid receptors (GR) stimulate absorption of Na+ by semicircular canal duct (SCCD) epithelia. In the present study, we sought to determine the presence of genes involved in the control of the amiloride-sensitive Na+ transport pathway in rat SCCD epithelia and whether their level of expression was regulated by glucocorticoids using quantitative real-time RT-PCR. Transcripts were present for alpha-, beta-, and gamma-subunits of the epithelial sodium channel (ENaC); the alpha1-, alpha3-, beta1-, and beta3-isoforms of Na+-K+-ATPase; inwardly rectifying potassium channels [IC50 of short circuit current (Isc) for Ba2+: 210 microM] Kir2.1, Kir2.2, Kir2.3, Kir2.4, Kir3.1, Kir3.3, Kir4.1, Kir4.2, Kir5.1, and Kir7.1; sulfonyl urea receptor 1 (SUR1); GR; mineralocorticoid receptor (MR); 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2; serum- and glucocorticoid-regulated kinase 1 (Sgk1); and neural precursor cell-expressed developmentally downregulated 4-2 (Nedd4-2). On the other hand, transcripts for the alpha4-subunit of Na+-K+-ATPase, Kir1.1, Kir3.2, Kir3.4, Kir6.1, Kir6.2, and SUR2 were found to be absent, and Isc was not inhibited by glibenclamide. Dexamethasone (100 nM for 24 h) not only upregulated the transcript expression of alpha-ENaC (approximately 4-fold), beta2-subunit (approximately 2-fold) and beta3-subunit (approximately 8-fold) of Na+-K+-ATPase, Kir2.1 (approximately 5-fold), Kir2.2 (approximately 9-fold), Kir2.4 (approximately 3-fold), Kir3.1 (approximately 3- fold), Kir3.3 (approximately 2-fold), Kir4.2 (approximately 3-fold), Kir7.1 (approximately 2-fold), Sgk1 (approximately 4-fold), and Nedd4-2 (approximately 2-fold) but also downregulated GR (approximately 3-fold) and 11beta-HSD1 (approximately 2-fold). Expression of GR and 11beta-HSD1 was higher than MR and 11beta-HSD2 in the absence of dexamethasone. Dexamethasone altered transcript expression levels (alpha-ENaC and Sgk1) by activation of GR but not MR. Proteins were present for the alpha-, beta-, and gamma-subunits of ENaC and Sgk1, and expression of alpha- and gamma-ENaC was upregulated by dexamethasone. These findings are consistent with the genomic stimulation by glucocorticoids of Na+ absorption by SCCD and provide an understanding of the therapeutic action of glucocorticoids in the treatment of Meniere's disease.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

[K+ and Ca++ currents in hair cells isolated from the semicircular canals of the frog].

Hair cells of the inner ear are endowed with different types of ionic channels. To characterize voltage- and ion-dependent channels in vestibular hair cells, experiments were performed in enzymatically isolated hair cells of frog semicircular canals by using the whole-cell configuration of the patch-clamp technique. A large outward current, identified as a K+ current, was recorded when 132 mM KCl were present in the pipette filling solution. It could be dissected pharmacologically into three different components. The first component, which was transient and selectively blocked by 10 mM external 4AP, is most likely an IA-type current. The second one, sensitive to 20 mM external TEA, might be a delayed rectifier K+ current, while the third component insensitive to TEA and showing faster activation time course has been interpreted as a K+ current of IKCa-type. After blocking the outward current by substituting Cs+ for K+ and adding 20 mM TEA to the internal solution, a sustained inward current, identified as a Ca++ current, could be recorded. This current did not inactivate, and was blocked by Cd++ more effectively than Ni++, thus suggesting the presence of Ca++ channels similar to the neuronal "L" channels. Since both K+ and Ca++ channels were recruited at potentials near the resting level, it is suggested that they are involved in the modulation of the resting as well as the evoked transmitter release from the basal pole of the hair cells.

4-Aminopyridine↗
PubMed2006

Superior semicircular canal dehiscence: oblique reformatted CT images for diagnosis.

PURPOSE: To retrospectively determine, by using thin-section multi-detector row computed tomography (CT), whether additional reformations in the planes of Stenver and Pöschl change the diagnostic interpretation for superior semicircular canal dehiscence (SSCD) when compared with the diagnostic interpretation of standard coronal reformations for SSCD. MATERIALS AND METHODS: Institutional review board approval was obtained, patient anonymity was maintained, and the study was HIPAA compliant. Twenty-seven patients (17 men, 10 women; average age, 45 years; range, 19-72 years) suspected of having SSCD who underwent temporal bone multi-detector row CT were retrospectively identified from electronic medical records. An additional 27 control subjects (nine men, 18 women; average age, 50 years; range, 18-87 years), who underwent temporal bone multi-detector row CT for other reasons, were retrospectively selected from the same period. Two neuroradiologists with certificates of added qualification, one with 5 years and one with 9 years of experience interpreting temporal bone CT images, independently reviewed the 108 temporal bones twice. One review was restricted to transverse images and coronal reformations. The other review used transverse images, coronal reformations, and oblique reformations in the planes of Stenver and Pöschl. The observers were blinded to clinical history, and the two reviews took place 3 months apart to avoid recall bias. The primary outcome measure was the intraobserver discordance rate between the two reviews. kappa Statistics were used to evaluate both intraobserver and interobserver variability. RESULTS: Observer 1 diagnosed SSCD in 25 of 108 (23%) temporal bones and had no discordances between the two reviews. Observer 2 diagnosed SSCD in 21 of 108 (19%) temporal bones and had one intraobserver discordance. After a post hoc consensus review of this one discordance, the radiologic diagnosis remained equivocal. The discordance involved the right temporal bone of a patient suspected of having SSCD in the left temporal bone, so no clinical follow-up was available. CONCLUSION: Coronal reformations from multi-detector row CT of the temporal bone are sufficient for the evaluation of SSCD. Additional reformations in the planes of Stenver and Pöschl do not change the radiologic diagnosis and may be reserved for equivocal or confusing cases.

Adolescent↗
PubMed2002

Argon laser irradiation of the semicircular canal in two patients with benign paroxysmal positional vertigo.

The results of long-term follow-up after surgical treatment of two patients with intractable benign paroxysmal positional vertigo are reported. Argon laser irradiation of the blue-lined posterior and lateral semicircular canals in one patient, and of only the posterior canal in the other was performed seven and six years ago, respectively. Argon laser irradiation was carried out 10 times in succession three mm along the canal to occlude it. The power applied each time was 1.5 W on the dial of the laser device for 0.5 sec. Relief of vertigo was noted on the second post-irradiation day. There has been no recurrence of vertigo in these patients.

Aged↗
PubMedDate not supplied

[Interaction between the otolithic organ and semicircular canals of the vestibular apparatus in the system of directional orientation of man in space].

A mathematical model is suggested of the biological system of angular stabilization in space relative to the local vertical using measures whose parameters are near to the parameters of the semicircular canals and otolithic organ of the man. On the basis of computer simulation for physiologically adequate external stimulations contribution of each of measures to the total process of angular stabilization is evaluated.

Humans↗
PubMed2001

Modal analysis of the diaphragm of the semicircular canal.

The aim of this paper is to determine the domain of validity of calculated quasi-static deformations of the cupula and of ciliar deflections on the crista ampullaris. Several three-dimensional models of the isolated ampullar diaphragm of the human semicircular canal and of that of the frog are studied theoretically by modal analysis. The four first modes of vibration are determined for each structure. Numerical simulations prove that for the first mode of vibration, the cupular deformation has the same shape as that obtained by applying a static pressure difference across the ampullar diaphragm. We studied also the effect of the mechanical properties (Young's modulus and Poisson's coefficient) of the components of the ampullar diaphragm on the vibration modes and their frequencies. The condition, which must be satisfied by the cupular internal viscosity, to have resonance near the natural frequency of the ampullar diaphragm is determined.

Animals↗
PubMed1989

Cupula displacement, hair bundle deflection, and physiological responses in the transparent semicircular canal of young eel.

The transparent labyrinth of young eels (Anguilla anguilla L.) was used in toto for studying the configuration of cupula displacement, deflection of the hair bundle, and correlated changes in transepithelial voltage (delta TEV) and nerve activity (delta NA) in the semicircular canal. Microcapillaries were introduced into the canal through holes produced by a microthermocauter. Mechanical stimulation was applied either by injection of fluid into the ampulla or by electromagnetically displacing ferrofluid as a piston within the canal. Motion of individual kinocilia, stained cupulae or the ferrofluid piston was analysed by double-exposed microphotographs, photodiodes, or a video-system. The three-dimensional cupula displacement configuration was found to be piston- to diaphragm-like. Hair bundles at different sites on the crista exhibit differences in amplitude and time course of deflection. The transfer factor between shifts of the canal fluid and the tips of the kinocilia is 0.4-0.6. Displacements in opposite directions induce delta TEV and delta NA of opposite sign. Various tests confirmed delta TEV to reflect receptor potential responses. Nerve activity adapts to a tonic response with a time constant of 6.4 s. No similar adaptation occurred in delta TEV. Stimulus-response curves of TEV- and NA-responses are similar and sigmoid in shape with saturation at ciliary deflections of roughly +6 degrees and -3 degrees.

Action Potentials↗
PubMed2000

Input of anterior and posterior semicircular canal interneurons encoding head-velocity to the dorsal Y group of the vestibular nuclei.

Neurons in the Y group of the vestibular nuclei are activated disynaptically from the ipsilateral VIIIth nerve and polysynaptically from the contralateral nerve. The ipsilateral anterior and posterior semicircular canals project to the Y group via interneurons in the vestibular nuclei. Candidate interneurons located in the rostrolateral corner of the superior (SVN) and in the caudal medial (MVN) vestibular nuclei were retrogradely labeled by the iontophoretic injection of biocytin into the Y group. The physiology of these interneurons named Y-group projecting neurons (YPNs) was studied in the SVN. SVN-YPNs were activated antidromically by electric pulse stimulation in the Y group. The properties of SVN-YPNs are distinct from those of SVN flocculus projecting neurons (FPNs). Namely, YPNs have a lower resting rate than FPNs, have more irregular interspike intervals, show a different phase and gain during the vestibuloocular reflex, and are located differentially within the SVN. After the injection of biocytin into the Y group, the locations of Purkinje cells that project to the Y group were confined to the vertical zones of the flocculus and ventral paraflocculus. However, mossy fibers originating in the Y group terminate in both the vertical and horizontal zones of the flocculus and ventral paraflocculus as well as in the ipsilateral nodulus.

Action Potentials↗
PubMed1976

Analysis of afferent responses from isolated semicircular canal of the guitarfish using rotational acceleration white-noise inputs. II. Estimation of linear system parameters and gain and phase spectra.

Quantitative estimates were computed for exponential coefficients and rate constants contributing to afferent unit impulse responses obtained from bundles innervating specific regions of the semicircular canal. The grouping of these estimates into specific response classes provided quantitative correlations with specific anatomical regions of innervation of the crista. Linear system gain and phase spectra were computed also, by applying Fourier transformations to unit impulse responses, for purposes of comparison with previous studies employing frequency domain analyses. Responses fitted by third-order linear system equations were specific to afferents innervating the crest and transition regions of the crista; whereas those fitted by overdamped, second-order equations were specific to afferents innervating the slopes and transition crista regions. It was concluded that strictly mechanical models of the transduction process are inadequate to account for the diverse and spatially distributed classes of observed responses and, moreover, structural features such as different hair cell types or efferent innervation effects could be excluded as inoperative in this preparation. The alternative hypothesis was suggested that certain of the observed subcomponents could be direct reflections of the initial mechanical stimulus, but that other subcomponents were reflections of more complex filtering mechanisms operating at the cellular or synaptic levels.

Animals↗
PubMedDate not supplied

The semicircular canals of the inner ear and the pneumatization of the temporal bone. A radioanatomic investigation.

In an investigation of 94 plastic casts of temporal bone specimens a wide range of variations both in the general outline of the pyramid and in the anatomy of its specific structures was found. Attempts were made to estimate the transverse and vertical dimensions of the petrous bone. Both the mastoid and the perilabyrinthine pneumatization correlated to the dimensions of some structures, but not to the size and shape of the semicircular canals.

Humans↗
PubMed2000

The effect of otolith and semicircular canal convergence on the VOR during eccentric rotation.

VOR gain modulation was systematically investigated in the Rhesus monkey (M. mulatta) during centric and variable eccentric (up to 50 cm) sinusoidal rotation (4 Hz, 0.75 degree) with the nose facing in- or outward to test convergence of otolith and semicircular canal afferences. Earth-stationary lit LED-targets were placed at different distances (12-180 cm) from the monkey. Results were compared to biological demands. During centric rotation at 4 Hz when smooth pursuit mechanisms do not play a role, VOR gain--as expected--was approximately 1 without dependence on target distance. Phase of VOR and centrifuge were shifted by about 180 degrees as was predicted. If the monkey was rotated eccentrically with the nose facing outward the expected gain enhancement for close targets was obtained. Maximal experimental VOR gain during 4 Hz rotation was 4.4 which was close to demand at 50 cm eccentricity and 15 cm target distance (predicted gain: 4.6). If the nose points inward three situations have to be distinguished from simulation: (1) target behind the axis of rotation--VOR gain decrement should occur; (2) target on the axis of rotation--"inverse VOR suppression"; (3) target between monkey and axis of rotation--phase reversal. Experimentally, VOR gain decrement was obtained (situation 1). VOR gain was minimal (but not zero) for targets around the axis of rotation (situation 2). Situation 3 has not been investigated in detail so far.

Acceleration↗
PubMed2006

Single-channel L-type Ca2+ currents in chicken embryo semicircular canal type I and type II hair cells.

Few data are available concerning single Ca channel properties in inner ear hair cells and particularly none in vestibular type I hair cells. By using the cell-attached configuration of the patch-clamp technique in combination with the semicircular canal crista slice preparation, we determined the elementary properties of voltage-dependent Ca channels in chicken embryo type I and type II hair cells. The pipette solutions included Bay K 8644. With 70 mM Ba(2+) in the patch pipette, Ca channel activity appeared as very brief openings at -60 mV. Ca channel properties were found to be similar in type I and type II hair cells; therefore data were pooled. The mean inward current amplitude was -1.3 +/- 0.1 (SD) pA at - 30 mV (n = 16). The average slope conductance was 21 pS (n = 20). With 5 mM Ba(2+) in the patch pipette, very brief openings were already detectable at -80 mV. The mean inward current amplitude was -0.7 +/- 0.2 pA at -40 mV (n = 9). The average slope conductance was 11 pS (n = 9). The mean open time and the open probability increased significantly with depolarization. Ca channel activity was still present and unaffected when omega-agatoxin IVA (2 microM) and omega-conotoxin GVIA (3.2 microM) were added to the pipette solution. Our results show that types I and II hair cells express L-type Ca channels with similar properties. Moreover, they suggest that in vivo Ca(2+) influx might occur at membrane voltages more negative than -60 mV.

Algorithms↗
PubMed2001

Changes in the vestibulo-ocular reflex after plugging of the semicircular canals.

The gain of the angular vestibulo-ocular reflex (aVOR) was determined in monkeys by rotation about a spatial vertical axis while upright or statically tilted forward and backward. Horizontal, vertical, and roll gains were determined at each head orientation and plotted as a function of head tilt. Before canal plugging, animals had maximal (spatial) horizontal gains when upright (spatial phase 0 degrees) and maximal roll gains when tilted forward or backward 90 degrees. Plugging caused striking changes in the characteristics of the aVOR gains at low frequencies. After plugging of the vertical canals, maximal horizontal and roll gains both occurred at head tilts of approximately 30 degrees forward. When the lateral canals were plugged, maximal horizontal and roll responses occurred when the head was tilted back approximately 50 degrees. The aVOR gains of the canal-plugged animals were also affected by stimulus frequency. In every instance, as stimulus frequency increased, the spatial phases shifted toward the normal response, that is, the response before plugging. This normalization effect was observed even in the animals with all six semicircular canals plugged, indicating that normalization was not due to spatial adaptation. A three-dimensional dynamic and kinematic model of the aVOR was able to account for all types of canal plugging by a simple change in the dominant time constant of the plugged canals from 3 s to 5 s to approximately 0.07 s. The model accurately predicted responses of the normal and canal-plugged animals at all frequencies. These data show that the central vestibular system does not spatially adapt to losses resulting from canal plugging.

Animals↗
PubMed1986

The commissural inhibition on secondary vestibulo-ocular neurons in the vertical semicircular canal systems in the cat.

The commissural inhibition on secondary vestibulo-ocular neurons (VOns) from the contralateral (c-) vertical canal system in the same geometric plane was studied in the anesthetized cat. The secondary VOns were identified by their orthodromic responses to stimulation of the ampullary nerves of the anterior (ACN) or posterior (PCN) semicircular canals and also by their antidromic responses to stimulation of the IIIrd and IVth nuclei. The majority of ACN-activated excitatory VOns in the descending and medial nuclei (32/36, 89%) and in the superior nucleus (20/23, 87%), received commissural inhibition from the c-PCN, while only few ACN-activated inhibitory VOns (3/35, 9%) in the superior nucleus received commissural inhibition from the c-PCN. On the other hand, all of the PCN-activated excitatory (50/50) and inhibitory (30/30) VOns in the vestibular nuclei received commissural inhibition following c-ACN stimulation.

Action Potentials↗
PubMed1976

Pathways for the vestibulo-ocular reflex excitation arising from semicircular canals of rabbits.

In anesthetized albino rabbits, ampullary branches of the vestibular nerve were stimulated electrically. Prominent and stable reflex contraction was induced in extra-ocular muscles by applying single current pulses of relatively long duration, 3-5 msec. Survey with a glass microelectrode revealed that, during application of relatively wide pulses to a canal, primary vestibular fibers discharged impulses repetitively at a rate as high as 300-1400/sec and that after being transmitted across second-order vestibular neurons these impulses built up summated EPSPs in oculomotor neurons, large enough to trigger off motoneuronal discharges. From each semicircular canal, prominent reflex contraction was evoked selectively in two muslces; from the anterior canal in the ipsilateral superior rectus and contralateral inferior oblique; from the horizontal canal in the ipsilateral medial rectus and contralateral lateral rectus; and from the posterior rectus. Acute lesion experiments indicated that signals for this excitation reached IIIrd and IVth nuclei via three different pathways; from the anterior canal through the ipsilateral brachium conjunctivum, from the horizontal canal through the ipsilateral fasciculus longitudinalis medialis and from the posterior canal through the contralateral fasciculus longitudinalis medialis.

Afferent Pathways↗
PubMed2006

Semicircular canal influence on the visually perceived eye level during gondola centrifugation.

BACKGROUND: When exposed to an increased gravitoinertial force, a subject, sitting upright, experiences an illusion of being tilted backwards. This so-called "G-excess illusion" is generally ascribed to the otolith organs. The present study aimed at elucidating how stimulation of the semicircular canals may influence the development of the G-excess illusion. METHODS: The visually perceived eye level (VPEL) was measured by means of a visual indicator in a large swing-out gondola centrifuge. The roll position of the gondola was controlled so that the subject was always upright with respect to the resultant vector of the Earth gravity force and the centrifugal force. Subjects (n = 8) underwent four centrifuge runs (2 G, 5 min), sitting in different positions, i.e., heading forwards, backwards, centripetally, and centrifugally. RESULTS: At the 2-G plateau there was a depression of the VPEL which was initially small but increased with a time constant of 90 +/- 30 s toward an asymptote of -22.0 +/- 6.9 degrees (mean and 1 SD for all positions). The initial depression was significantly smaller for the centripetal (+2.0 +/- 14.6 degrees) than for the centrifugal position (-14.5 +/- 10.4 degrees). However, there was no difference between the forward (-5.6 +/- 4.8 degrees) and backward (-4.0 +/- 4.5 degrees) positions. Initially after deceleration of the centrifuge to 1 G there was still a significant depression of the VPEL (-13.5 +/- 7.9 degrees), decreasing with a time constant of 100 +/- 46 s. CONCLUSIONS: The considerable delay in the otolith-mediated changes in the VPEL is interpreted as due to the absence of adequate canal information for a change in head position. The difference in VPEL between the centripetal and centrifugal positions suggests an influence of canal change-in-position information. However, pitch-plane angular velocity, being of considerable magnitude but of opposite sign for the forward and backward positions, did not influence the VPEL.

Acceleration↗
PubMed2003

Superior semicircular canal dehiscence simulating otosclerosis.

This is a report of a patient with an air-bone gap, thought 10 years ago to be a conductive hearing loss due to otosclerosis and treated with a stapedectomy. It now transpires that the patient actually had a conductive hearing gain due to superior semicircular canal dehiscence. In retrospect for as long as he could remember the patient had experienced cochlear hypersensitivity to bone-conducted sounds so that he could hear his own heart beat and joints move, as well as a tuning fork placed at his ankle. He also had vestibular hypersensitivity to air-conducted sounds with sound-induced eye movements (Tullio phenomenon), pressure-induced nystagmus and low-threshold, high-amplitude vestibular-evoked myogenic potentials. Furthermore some of his acoustic reflexes were preserved even after stapedectomy and two revisions. This case shows that if acoustic reflexes are preserved in a patient with an air-bone gap then the patient needs to be checked for sound- and pressure-induced nystagmus and needs to have vestibular-evoked myogenic potential testing. If there is sound- or pressure-induced nystagmus and if the vestibular-evoked myogenic potentials are also preserved, the problem is most likely in the floor of the middle fossa and not in the middle ear, and the patient needs a high-resolution spiral computed tomography (CT) of the temporal bones to show this.

Aged↗