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[An experimental study on the inhibitory response of the frog semicircular canal nerve].

The inhibitory response of the posterior semicircular canal (p.s.c.) ampullary nerve was studied in comparison with the excitatory response. The isolated p.s.c. of the bull frog was stimulated by the mechanical endolymphatic flow toward either the ampullofugal (AF, excitatory) or the ampullopetal (AP, inhibitory) direction. Three experiments were performed. 1) Experiment I: The influence of the endolymphatic K+ concentration. In both the high (50mM) and the low (2.5mM) K+ environment, the inhibitory response was smaller than the excitatory response. This was more pronounced in the low K+ environment. 2) Experiment II: The influence of the initial position of the cupula. The magnitudes of the responses when the cupula was moved from various positions were compared. When the same amount of stimulus was given in the same direction, the responses were equal regardless of the initial position of the cupula. The inhibitory response yielded a time constant approximately 2-3 times as long as the excitatory response. 3) Experiment III: The interaction of the AF and the AP stimulus. The influence of the inhibitory response upon the following excitatory response and vice versa, were studied by changing the timing of the stimulus onset. Both the action potential and the DC potential were recorded for comparison. The AP stimulus which immediately followed the AF stimulus suppressed the action potential and the negative DC potential was observed. On the other hand the AF stimulus which immediately followed the AP stimulus gave rise to the distinct positive DC potential but the action potential could hardly be evoked. That AF stimulus resulted in different responses between the action potential and the DC potential indicates that the DC potential recorded in this study is possibly a generator potential.

Action Potentials↗

Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel.

The semicircular canal duct (SCCD) epithelium is a vestibular epithelial domain that was recently shown to actively contribute to endolymph homeostasis by Cl(-) secretion under control of beta(2)-adrenergic stimulation. By analogy to other Cl(-) secretory epithelia, we hypothesized that SCCD also provides an active absorptive pathway for Na(+) under corticosteroid control. Measurements of short-circuit current (I(sc)) demonstrated stimulation (7-24 h) by the glucocorticoids hydrocortisone (EC(50) 13 nM), corticosterone (33 nM), prednisolone (70 nM), and dexamethasone (13 nM) over physiologically and therapeutically relevant concentrations and its block by amiloride (IC(50) 470 nM) and benzamil (57 nM), inhibitors of the epithelial sodium channel (ENaC). I(sc) was also partially inhibited by basolateral ouabain and Ba(2+), indicating the participation of Na(+)-K(+)-ATPase and a K(+) channel in Na(+) transport. By contrast, aldosterone stimulated I(sc) only at unphysiologically high concentrations (EC(50) 102 nM). The action of all steroids was blocked by mifepristone (RU-486; K(d) approximately 0.3 nM) but not by spironolactone (K(d) approximately 0.7 microM). Expression of mRNA for the alpha-, beta-, and gamma-subunits of ENaC was demonstrated in the presence and absence of glucocorticoids. These findings are the first to identify SCCD in the vestibular labyrinth as a site of physiologically significant ENaC-mediated Na(+) absorption and osmotically coupled water flux. They further demonstrate regulation of Na(+) transport by natural and therapeutic glucocorticoids. The results provide for the first time an understanding of the therapeutic benefit of glucocorticoids in the treatment of Meniere's disease, a condition that is associated with increased luminal fluid volume.

Animals↗

N-ethylmaleimide-inhibited electrogenic K+ secretion in the ampulla of the frog semicircular canal.

1. The mechanisms of K+ secretion into endolymph were studied on a preparation of isolated semicircular canal with different pharmacological inhibitors. Three periods of 5 or 30 min were performed, the first as control, the second in the presence of the drugs added to the apical or the basolateral bathing solution, and the third as recovery. Apical fluid was sampled at the beginning and the end of each period, transepithelial potential was recorded, Na+, K+, and Cl- concentrations, and K+ efflux, with 86Rb+ as a tracer, were measured and K+ fluxes were calculated. 2. When both sides of the epithelium were bathed with perilymph-like solution, the epithelium absorbed Na+, secreted K+, and generated a lumen positive potential. 3. The ATPases inhibitors, ouabain (10(-5) and 10(-3) M) and N-ethylmaleimide (10(-4) and 10(-3) M) inhibited the electrogenic K+ secretion when added to the basolateral fluid. N-ethylmaleimide (10(-3) M) applied to the apical fluid during a 5 min period decreased the K+ influx by 43% and the transepithelial potential by 66%. Other ATPase inhibitors, harmaline (10(-3) M), omeprazole (10(-4) M), vanadate (10(-4) M and 10(-3) M), N,N'-dicyclohexylcarbodiimide (DCC, 10(-5) M), 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl, 5 x 10(-6) M and 5 x 10(-5) M), and bafilomycin (10(-7) M) did not affect the K+ transport nor the transepithelial potential when they were added to the apical fluid. 4. The Na(+)-K(+)-Cl- co-transporter inhibitor, bumetanide, decreased both the transepithelial potential and the K+ transport when added to the basolateral solution but not to the apical one. At 10(-6) M, bumetanide maximally decreased the K+ influx by about 60%. 5. K+ channel blockers, quinine (10(-4) M), TEA (5 x 10(-3) M), added to the apical solution and barium (2 x 10(-3) M) added to either the apical or the basolateral solutions, did not affect the K+ transport and the transepithelial potential. 6. The carbonic anhydrase inhibitor acetazolamide (10(-3) M) added to both apical and basolateral solutions did not affect the K+ transport and the transepithelial potential. 7. It is concluded that, in the ampulla of the semicircular canal, a basolateral Na(+)-K(+)-Cl- co-transporter energized by the Na+, K(+)-ATPase was involved for 60% in the K+ secretion into endolymph. The electrogenic K+ transport would partly depend on a N-ethylmaleimide-sensitive protein possibly located at the apical plasma membrane or intracellularly.

Animals↗

[Dehiscence of the superior semicircular canal: report of a case and bibliography review].

We present a case of deficiency of the superior semicircular canal (SSCD) in a 37 years old patient that came to us because of episodes of subjective vertigo in response to intense sounds (Tullio phenomenon). The audiometry, electronistagmography, timpanometry and stapes reflexes were normal and the fistula test was negative. The CT scan showed an absence of bone overlying the superior semicircular canal (SSC) of the right ear and the left ear was normal. When both ears were exposed to intense sounds, only the right one presented vertigo was, without nystagmus.

Adult↗

[Analysis of auditory steady-state response to multiple simultaneous stimuli and cochlea morphology in guinea pigs with posterior semicircular canal fistula].

OBJECTIVE: To observe the changes of auditory steady-state response (ASSR) threshold in guinea pigs with posterior semicircular canal fistula. METHODS: In 10 guinea pigs, a window was opened in the posterior semicircular canal of the left ear with the right ear serving as the control for testing the ASSR under anesthesia with pentobarbital sodium. RESULTS: The mean and standard deviation of ASSR threshold (dB SPL) at 0.5, 1, 2, and 4 kHz in the left ear was 35.00+/-14.33, 25.50+/-12.37, 20.00+/-9.37 and 20.00+/-9.18, respectively, and was 31.00+/-16.19, 25.50+/-12.34, 18.00+/-6.96 and 18.50+/-6.71 in the right ear, respectively. Paired-sample t test showed no significant difference in the ASSR at the same frequency between the two ears. CONCLUSION: Small fistula by surgery causes no significant hearing loss in guinea pigs.

Animals↗

Semicircular canal contribution to the perception of roll tilt during gondola centrifugation.

BACKGROUND: Spatial disorientation is an important problem in aviation. The mechanisms behind the sensation of roll tilt during coordinated turns are not well known. The present study aimed at elucidating what kind of semicircular canal information might cause tilts of the subjective horizontal during gondola centrifugation. METHODS: The subjective visual horizontal (SVH) was measured by means of an adjustable visual line in darkness. Subjects (n = 8) underwent four centrifuge runs (2 G, 5 min), sitting in different positions, i.e., heading forwards, backwards, centripetally, and centrifugally. The roll position of the gondola (60 degrees at 2 G) was controlled so that the subject was always upright with respect to the resultant gravitoinertial force vector. Thus, the semicircular-canal stimulus components in yaw, pitch, and roll were varied to some extent independently of each other. RESULTS: For the forward position the SVH was substantially tilted in a direction compensatory with respect to the inclination of the gondola. For the backward position there was also a tendency to a compensatory SVH tilt. In all subjects the magnitude of tilt was larger for the forward position than for the backward. The group means were +20.9 +/- 8.4 degrees and -6.9 +/- 10.5 degrees (positive sign designates a clockwise deviation of the SVH), p < 0.001, n = 8. There were no significant SVH tilts for the centripetal (+6.4 +/- 10.7 degrees) and centrifugal (+2.1 +/- 4.8 degrees) positions. The effects of deceleration of the centrifuge were very small for all positions. CONCLUSION: These findings suggest that the substantial SVH tilt after acceleration heading forwards is not directly related to any single component of semicircular canal stimulation but depends on the ability of the brain to expediently process complex stimulus patterns.

Adult↗

Spatial position of the lateral semicircular canal in 14--60-day-old rat heads.

During growth the rat skull straightens considerably due to flexions between skull parts and individual bones. This straightening is defined as orthocephalization. Orthocephalization might also be caused by a change in head posture during growth, i.e. it may be "apparent". In order to study the significance of this phenomenon, radiographs of dried skulls of male rats, 14, 30 and 60 d of age were subjected to angular measurements between the plane of the lateral semicircular canal and the plane of foramen magnum and of the basisphenoid bone, respectively. When the plane of the lateral semicircular canal is placed horizontally, the head is claimed to be in natural position. No changes in the angulation between the lateral semicircular canal and the basisphenoid bone could be revealed, whereas the foramen magnum was shown to rotate upwards and backwards in relation to the plane of the canal. This implies that the orthocephalization which takes place between 14 and 60 d is caused only by angular changes, and that no apparent changes occur due to changes in head posture.

Age Factors↗

[Responses of the units of the nerve of the frog semicircular canal to caloric stimuli of changing amplitude].

In curarized frogs, responses of isolated neural units of the lateral semicircular canal (LSC) to short local caloric stimuli of different amplitudes (0.5--12.0 degrees C over the canal temperature) inducing excitatory current of endolymph in the LSC, were studied. Estimation of maximal (peak) frequences (PF) in the responses showed the PFs in responses of 52% units (group A) to be either linearly or semilogarithmically related to peak temperature (PT). In 22% units (group B), PFs revealed saturation at PT8--12 degrees C. In 25% units (group C) PFs were related to PT first in direct and then--along with increase of PT--in reverse proportion. Duration of the group A responses is linearly for semilogarithmically related to PT. This was not observed in groups B and C. Two cases of correlation between spontaneous activity and dynamic characteristics of units from groups A and C were found. The results are in agreement with the literature references concerning data obtained in frogs using angular acceleration and stop-stimuli. The controlled caloric stimulus was concluded to be convenient for studying the dynamic characteristics of the semicircular canals afferents.

Acceleration↗

Spatial transformation of semicircular canal signals into abducens motor signals. A comparison between grass frogs and water frogs.

The spatial transformation of semicircular canal signals to extraocular motor signals was studied by recording abducens nerve responses in grass and water frogs. Both species have similar vestibular canal coordinates but dissimilar orientations of their optic axes. Before sinusoidal oscillation in darkness the static head position was systematically altered to determine the planes of head oscillation in pitch and roll associated with minimal abducens nerve responses. Measured data and known canal plane vectors were used to calculate the abducens response vector in canal coordinates. The abducens vector deviated from the horizontal canal plane vector in grass frogs by 15 degrees and in water frogs by 34 degrees but was aligned with the pulling direction of the lateral rectus muscle in each of the two species. Lesion experiments demonstrated the importance of convergent inputs from the contralateral horizontal and anterior semicircular canals for the orientation of the abducens response vector. Thus, the orientation of the optic axis and the pulling directions of extraocular muscles are taken into account by the central organization of vestibulo-ocular reflexes. Horizontal and vertical canal signals are combined species-specifically to transform the spatial coordinates of sensory signals into appropriate extraocular motor signals.

Abducens Nerve↗

The origin of slow potentials in semicircular canals of the frog.

Slow potentials generated in the sensory organ of the ampulla were recorded in isolated semicircular canals of the frog by means of fluid electrodes. These potentials, which may be picked up from the intrampullar fluid and those from the ampullar nerve appear to be generated at different stages of the process taking place in crista ampullaris. Slow intra-ampullar potentials apparently reflect receptor potentials of hair cells. They are preserved after degeneration of the nerve fibre endings and are relatively insensitive to DNP poisoning; their amplitude is maximum at high K+ concentrations. Slow nerve potentials appear to be due to electronic spreading of post-synaptic excitatory potentials generated at cytoneural junctions. They disappear after degeneration of the nerve fibres, in low Ca++ and high Mg++ solutions and are extremely sensitive to DNP poisoning. An analysis of the time-course of the slow ampullar and nerve potentials referred to the discharge of impulses in afferent fibres was performed with a view to interpreting the transduction mechanism of semicircular canals.

Animals↗

Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal.

Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

Animals↗

Sympathetic nerve activity during natural stimulation of horizontal semicircular canals in humans.

We have shown that static head-down neck flexion elicits increases in muscle (MSNA) but not skin sympathetic nerve activity (SSNA) in humans. These findings suggest that stimulation of the otolith organs causes differential sympathetic outflow to vascular beds. The purpose of the present study was to determine whether yaw head rotation (YHR), which stimulates the horizontal semicircular canals, elicits sympathetic nerve responses. To test this question, we recorded MSNA (n = 33) and SSNA (n = 25) before and during 3 min of sinusoidal YHR performed at 0.1, 0.6, and 1.0 Hz. At all frequencies, YHR elicited no significant changes in heart rate and mean arterial pressure. Likewise, YHR did not significantly change either MSNA or SSNA at all frequencies. Our results indicate that stimulation of the horizontal semicircular canals by YHR does not alter SNA to either muscle or skin. Moreover, these results provide evidence to support the concept that the otolith organs but not the horizontal semicircular canals participate in the regulation of SNA in humans.

Adult↗

Responses of irregularly discharging chinchilla semicircular canal vestibular-nerve afferents during high-frequency head rotations.

Mammalian vestibular-nerve afferents innervating the semicircular canals have been divided into groups according to their discharge regularity, gain at 2-Hz rotational stimulation, and morphology. Low-gain irregular afferents terminate in calyx endings in the central crista, high-gain irregular afferents synapse more peripherally in dimorphic (bouton and calyx) endings, and regular afferents terminate in the peripheral zone as bouton-only and dimorphic endings. The response dynamics of these three groups have been described only up to 4 Hz in previous studies. Reported here are responses of chinchilla semicircular canal vestibular-nerve afferents to rotational stimuli at frequencies up to 16 Hz. The sensitivity of all afferents increased with increasing frequency with the sensitivity of low-gain irregular afferents increasing the most and matching the high-gain irregular afferents at 16 Hz. All afferents increased their phase lead with respect to stimulus velocity at higher frequencies with the highest leads in low-gain irregular afferents and the lowest in regular afferents. No attenuation of sensitivity or shift in phase consistent with the presence of a high-frequency pole over the range tested was noted. Responses were best fit with a torsion-pendulum model combined with a lead operator (tau(HF1)s + 1)(tau(HF2)s + 1). The discharge regularity of individual afferents was correlated to the value of each afferent's lead operator time constants. These findings suggest that low-gain irregular afferents are well suited for encoding the onset of rapid head movements, a property that would be advantageous for initiation of reflexes with short latency such as the vestibulo-ocular reflex.

Animals↗

Combined perilymphatic fistulas of the round window and lateral semicircular canal. A report of 2 cases.

Two patients with combined perilymphatic fistulas of both the round window and the lateral semicircular canal are presented. They became asymptomatic only when both fistulas were closed. In both cases the hearing improved concurrently. It is recommended that when a traumatic perilymphatic fistula is not cured by closing window fistulas, the lateral semicircular canal be explored.

Adult↗

Dehiscence or thinning of bone overlying the superior semicircular canal in a temporal bone survey.

OBJECTIVE: To determine the incidence and etiology of dehiscences of bone overlying the superior semicircular canal in a temporal bone archive. DESIGN: A microscopic study was performed of 1000 temporal bones from 596 adults in a university hospital registry. Specimens were sectioned vertically in the plane of the superior semicircular canal. Measurements of minimum bone thickness over the superior canal were made in a subset of 108 randomly chosen specimens. All bones were examined for thinning or dehiscence relative to these norms. Clinical histories, when available, were reviewed. RESULTS: Complete dehiscence of the superior canal was identified in 5 specimens (0.5%), at the middle fossa floor (n = 1) and where the superior petrosal sinus was in contact with the canal (n = 4). In 14 other specimens (1.4%), the bone at the middle fossa floor (n = 8) or superior petrosal sinus (n = 6) was no thicker than 0.1 mm, significantly less than values measured in the control specimens (P<.001). Abnormalities were typically bilateral. Specimens from infants demonstrated uniformly thin bone over the superior canal in the middle fossa at birth, with gradual thickening until 3 years of age. CONCLUSIONS: Dehiscence of bone overlying the superior canal occurred in approximately 0.5% of temporal bone specimens (0.7% of individuals). In an additional 1.4% of specimens (1.3% of individuals), the bone was markedly thin (< or =0.1 mm), such that it might appear dehiscent even on ultra-high-resolution computed tomography of the temporal bone. Sites affected were in the middle fossa floor or a deep groove for the superior petrosal sinus, often bilaterally. These abnormalities may arise from failure of postnatal bone development. Thin areas of bone over the superior canal may be predisposed to disruption by trauma.

Adult↗

Pharmacological characterization of ATP receptors in ampulla from frog semicircular canal.

Phosphoinositidase C activities sensitive to purine and pyrimidine nucleotides have been identified earlier in ampulla from Rana ridibunda semicircular canal. The aim of this study was to characterize the pharmacological properties of other P2 receptors borne by this structure. A microassay was developed to measure the binding of [35S]adenosine 5'-O-(2-thiodiphosphate) ([35S]ADPbetaS) to a few ampullas microdissected from frog semicircular canals. When determined at 4 degrees C in the absence of divalent cations, [35S]ADPbetaS binding was saturable with incubation time and reversible after elimination of free radioligand. The dissociation kinetics were biphasic and comprised a major component that was rapidly reversible and a minor component that dissociated slowly. [35S]ADPbetaS binding was competitively inhibited by unlabeled ADPbetaS with an apparent dissociation constant of 0.48 +/- 0.09 microM and a Hill coefficient of 0.70 +/- 0.06, and Scatchard analysis revealed a minor class of high-affinity binding sites (RT1 = 52 +/- 11 fmol [35S]ADPbetaS bound/ampulla and Kd1 = 0.15 +/- 0.04 microM) and a major class of low-affinity binding sites (RT2 = 436 +/- 79 fmol [35S]ADPbetaS bound/ampulla and Kd2 = 2.0 +/- 0.8 microM). The pattern of stereospecificity for recognition of unlabeled structural ATP analogs was ADPbetaS >/= alpha, beta-methyleneadenosine 5'-triphosphate = ADP = adenosine 5'-O-(3-thiotriphosphate) > ATP = diadenosine tetraphosphate = AMP > 2'- and 3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate >/= 2-methylthioadenosine 5'-triphosphate > 2-desoxythymidine 5'-triphosphate = guanosine 5'-triphosphate = inosine-5'-triphosphate = xanthosine 5'-triphosphate = cytosine 5'-triphosphate = uridine 5'-triphosphate = uridine-5'-diphosphate, whereas cAMP and adenosine were devoid of activity. For antagonists, suramin revealed competitive inhibitor potencies, whereas reactive blue 2 and DIDS acted as pure noncompetitive inhibitors. Results suggest that the population of labeled receptors is heterogeneous and contains a low number of P2Y-like receptors and a large number of P2X-like receptors whose molecular subtypes and functions in endolymph homeostasis remain to be defined.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Vestibular destruction by slow infusion of gentamicin into semicircular canals.

Intratympanic or round window application of gentamicin is often used to alleviate disabling vertigo arising from unilateral Meniere's disease; however, treatment is often accompanied by hearing loss because the drug initially enters the cochlea before diffusing to the vestibular system. In order to enhance vestibular damage and reduce the risk of hearing loss, gentamicin was infused directly into the vestibular system. An osmotic pump containing 50, 100, 200 or 400 microg/ml of gentamicin was infused into the superior semicircular canal of the chinchilla for 7 days. Afterwards, vestibular damage was evaluated by measuring the decline in hair cell density in the utricle, saccule and superior semicircular canals. Auditory damage was assessed with distortion product otoacoustic emissions (DPOAE) and outer hair cell (OHC) and inner hair cell (IHC) loss. Infusion with the two lowest gentamicin concentrations resulted in significant hair cell loss and reduced duration of the nystagmus response, but had little or no effect on OHC or DPOAE. Higher doses of gentamicin damaged cochlear hair cells and reduced the DPOAE. In conclusion, slow infusion of a low dose of gentamicin into the semicircular canals mainly damages the vestibular hair cells and inactivates the nystagmus response without damaging cochlear hair cells or DPOAE.

Animals↗