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At least 523 records · Page 29Linked to original sources
PubMed2006

Separate Na,K-ATPase genes are required for otolith formation and semicircular canal development in zebrafish.

We have investigated the role of Na,K-ATPase genes in zebrafish ear development. Six Na,K-ATPase genes are differentially expressed in the developing zebrafish inner ear. Antisense morpholino knockdown of Na,K-ATPase alpha1a.1 expression blocked formation of otoliths. This effect was phenocopied by treatment of embryos with ouabain, an inhibitor of Na,K-ATPase activity. The otolith defect produced by morpholinos was rescued by microinjection of zebrafish alpha1a.1 or rat alpha1 mRNA, while the ouabain-induced defect was rescued by expression of ouabain-resistant zebrafish alpha1a.1 or rat alpha1 mRNA. Knockdown of a second zebrafish alpha subunit, alpha1a.2, disrupted development of the semicircular canals. Knockdown of Na,K-ATPase beta2b expression also caused an otolith defect, suggesting that the beta2b subunit partners with the alpha1a.1 subunit to form a Na,K-ATPase required for otolith formation. These results reveal novel roles for Na,K-ATPase genes in vestibular system development and indicate that different isoforms play distinct functional roles in formation of inner ear structures. Our results highlight zebrafish gene knockdown-mRNA rescue as an approach that can be used to dissect the functional properties of zebrafish and mammalian Na,K-ATPase genes.

Animals↗
PubMed1988

Histamine and related substances influence neurotransmission in the semicircular canal.

Histamine and other imidazole-containing substances were found to increase ampullar nerve afferent firing rate while both H1 and H2 histamine antagonists effectively inhibited ampullar nerve activity. A specific inhibitor of histidine decarboxylase, the enzyme which catalyses the synthesis of histamine, reduced ampullar nerve firing in a dose-dependent manner. These observations suggest a physiological role for histamine in the inner ear. Maintenance of a response to histamine after de-efferentation of the crista ampullaris supports the hypothesis that the site of action is the hair cell; antagonism of the histamine response by a cholinergic antagonist, atropine, and antagonism of a cholinergically mediated facilitation by the histaminergic antagonist pyrilamine, indicate that the site of action may involve the acetylcholine receptor complex on the crista ampullaris hair cells. The observation that imidazole-containing compounds cause significant effects on semicircular canal neurotransmission provides an important finding with regard to the site of action of antihistamines used for the treatment of vertigo and motion sickness.

Animals↗
PubMed1986

Validity of Ewald's law in the horizontal semicircular canals and the vestibular nuclei: electron microscopic observation and quantitative [14C]-2-deoxy-D-glucose study.

Two series of experiments were performed by using a total of 36 guinea pigs. The 1st series was to compare the influence of rotatostimulation on the bilateral cristae ampullare. After repeating the rotatostimulation with the cupulometric mode (the terminal turning velocity: 450 degrees/sec) for 48 hr, ultrastructural changes of sensory cells were found in 9 of 17 animals with transmission electron microscopy. They showed stronger influences on the ampullopetal flow side with the exception of one animal. In the 2nd series, the difference in excitability between the bilateral vestibular nuclei was investigated on 6 guinea pigs which were exposed to the clockwise constant angular acceleration of 1 degree/sec2 for 8 min. The autoradiographic study with [14C]-2-deoxy-D-glucose (the 2-DG) revealed that the rotation-induced glucose uptake was increased significantly in the superior and the medial vestibular nuclei of the ampulloptal flow side. The results of the two series of experiments suggest the predominance of the ampullopetal effect not only in the horizontal semicircular canals but also in the vestibular nuclei.

Animals↗
PubMed1998

Nkx5-1 controls semicircular canal formation in the mouse inner ear.

The inner ear develops from the otic vesicle, a one-cell-thick epithelium, which eventually transforms into highly complex structures including the sensory organs for balance (vestibulum) and hearing (cochlea). Several mouse inner ear mutations with hearing and balance defects have been described but for most the underlying genes have not been identified, for example, the genes controlling the development of the vestibular organs. Here, we report the inactivation of the homeobox gene, Nkx5-1, by homologous recombination in mice. This gene is expressed in vestibular structures throughout inner ear development. Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resemble the typical hyperactivity and circling movements of the shaker/waltzer type mutants. The balance defect correlates with severe malformations of the vestibular organ in Nkx5-1(-/-) mutants, which fail to develop the semicircular canals. Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian vestibular system.

Animals↗
PubMed2005

Neuronal calcium sensor-1 gene ncs-1a is essential for semicircular canal formation in zebrafish inner ear.

We have analyzed the functional role of neuronal calcium sensor-1 (Ncs-1) in zebrafish development. We identified two orthologs of the mammalian NCS-1 gene. Full-length cDNAs encoding zebrafish Ncs-1a and Ncs-1b polypeptides were cloned and characterized. Whole-mount in situ hybridization revealed that ncs-1a mRNA was expressed beginning at early somitogenesis. As development progressed, ncs-1a mRNA was present throughout the embryo with expression detected in ventral hematopoietic mesoderm, pronephric tubules, CNS nuclei, and otic vesicle. By 4.5 days post fertilization (dpf), ncs-1a expression was detected primarily in the brain. Expression of ncs-1b mRNA was first detected at 36 hours post fertilization (hpf) and was restricted to the olfactory bulb. By 4.5 dpf, ncs-1b was expressed at low levels throughout the brain. Knockdown of ncs-1a mRNA translation with antisense morpholinos blocked formation of semicircular canals. These studies identify a novel function for ncs-1a in inner ear development and suggest that this calcium sensor plays an important role in vestibular function.

Amino Acid Sequence↗
PubMed2005

[Time-dependent vestibular function loss of semicircular canals and otolith organs in Menière's disease].

INTRODUCTION: Since Dohlmann's investigations the extremely variable interindividual natural course of Menière's disease has been documented. The description of sub-entities of Menière's disease shows, the localisation of dysfunction within the labyrinth is of considerable importance. The selective investigation of crista and macula sensor organs and its time-dependent progression even provides information for the disease's staging. METHODS: In the retrospective trial presented here, 126 patients suffering from vertigo were tested by the methods described above. 10 of these patients who showed a triad of symptoms including vertigo attacks, unilateral sudden hearing loss and tinnitus were selected for this study. All 10 patients were tested within 48 hours after the last acute vertigo attack by means of caloric irrigation and VEMPs. RESULTS: The function loss verified in saccular testing could be found in Menière's disease progression at an earlier stage than the utricular function loss. Most patients with a long history of vertigo attacks also suffered from a dysfunction of the semicircular canals. DISCUSSION: The differential testing of the otolith function is a valid tool for the recognition of early labyrinth dysfunction in Menière's disease and could lead to an earlier onset of specific therapy. It also provides the base for a differentiated staging prior to therapy planning.

Adolescent↗
PubMedDate not supplied

The influence of semicircular canal morphology on endolymph flow dynamics. An anatomically descriptive mathematical model.

The classic Steinhausen/Groen mathematical description of endolymph flow in a toroidal semicircular canal is extended to the case where the size, shape, and curvature of the canal lumen change continuously through the duct, utricle, and ampulla. The resulting second-order differential equation has three coefficients, unlike the equation of a torsion pendulum, which has only two. The salient anatomical parameters which determine endolymph motion are: the length of the central streamline occupying the center of the canal lumen; the area enclosed by this streamline as projected into the plane of rotation; the average inverse cross-sectional area of the lumen (taken around the central streamline); and the average inverse squared cross-sectional area, weighted by a local wall shape factor. These parameters are evaluated and the average displacement of the face of the cupula is estimated for the human, guinea pig, and rat, based on new anatomical data presented in companion papers. The model predicts that the dynamic range of human average cupula motion lies between 520 A and 10 microns.

Animals↗
PubMed1997

Three-dimensional analysis of vestibular efferent neurons innervating semicircular canals of the gerbil.

Anterograde labeling techniques were used to examine peripheral innervation patterns of vestibular efferent neurons in the crista ampullares of the gerbil. Vestibular efferent neurons were labeled by extracellular injections of biocytin or biotinylated dextran amine into the contralateral or ipsilateral dorsal subgroup of efferent cell bodies (group e) located dorsolateral to the facial nerve genu. Anterogradely labeled efferent terminal field varicosities consist mainly of boutons en passant with fewer of the terminal type. The bouton swellings are located predominately in apposition to the basolateral borders of the afferent calyces and type II hair cells, but several boutons were identified close to the hair cell apical border on both types. Three-dimensional reconstruction and morphological analysis of the terminal fields from these cells located in the sensory neuroepithelium of the anterior, horizontal, and posterior cristae were performed. We show that efferent neurons densely innervate each end organ in widespread terminal fields. Subepithelial bifurcations of parent axons were minimal, with extensive collateralization occurring after the axons penetrated the basement membrane of the neuroepithelium. Axonal branching ranged between the 6th and 27th orders and terminal field collecting area far exceeds that of the peripheral terminals of primary afferent neurons. The terminal fields of the efferent neurons display three morphologically heterogeneous types: central, peripheral, and planum. All cell types possess terminal fields displaying a high degree of anisotropy with orientations typically parallel to or within +/-45 degrees of the longitudinal axis if the crista. Terminal fields of the central and planum zones predominately project medially toward the transverse axis from the more laterally located penetration of the basement membrane by the parent axon. Peripheral zone terminal fields extend predominately toward the planum semilunatum. The innervation areas of efferent terminal fields display a trend from smallest to largest for the central, peripheral, and planum types, respectively. Neurons that innervate the central zone of the crista do not extend into the peripheral or planum regions. Conversely, those neurons with terminal fields in the peripheral or planum regions do not innervate the central zone of the sensory neuroepithelium. The central zone of the crista is innervated preferentially by efferent neurons with cell bodies located in the ipsilateral group e. The peripheral and planum zones of the crista are innervated preferentially by efferent neurons with cell bodies located in the contralateral group e. A model incorporating our anatomic observations is presented describing an ipsilateral closed-loop feedback between ipsilateral efferent neurons and the periphery and an open-loop feed-forward innervation from contralateral efferent neurons. A possible role for the vestibular efferent neurons in the modulation of semicircular canal afferent response dynamics is proposed.

Animals↗
PubMed2003

A pharmacologically distinct nicotinic ACh receptor is found in a subset of frog semicircular canal hair cells.

Frog vestibular organs are endowed with a prominent cholinergic efferent innervation whose stimulation results in several different effects, thereby suggesting diversity in the expression of postsynaptic acetylcholine (ACh) receptors. The application of ACh can mimic efferent stimulation in producing both an inhibition and a facilitation of afferent discharge which are thought to be mediated by at least two distinct ACh receptors present on vestibular hair cells, i.e., alpha9-containing nicotinic receptors (alpha9nAChR) and muscarinic receptors (mAChR), respectively. Using patch-clamp and multiunit vestibular afferent recordings, we demonstrate the presence of an additional excitatory hair cell nicotinic ACh receptor pharmacologically distinct from both alpha9nAChR and mAChR. In order of increasing potency, this distinct receptor was activated by ACh, carbachol, and particularly by the selective nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP). This DMPP-sensitive nicotinic receptor (RDMPP) was antagonized by the classic nicotinic antagonist d-tubocurarine, but refractory to strychnine, atropine, and propylbenzilylcholine mustard, at concentrations that completely block alpha9nAChR and/or mAChR. Activation of RDMPP on application of ACh or DMPP to a subpopulation of isolated posterior semicircular canal (SCC) hair cells resulted in a large depolarization (18.0 +/- 1.2 mV). The current underlying this depolarization was typically small (80.1 +/- 21.6 pA) and showed an inward rectification starting around -45 mV. Given their respective EC50s (47 nM vs. 20 microM), RDMPP was nearly 400 times more sensitive to ACh than alpha9nAChR and thus responded to concentrations of ACh considered too low to be effective at stimulating alpha9nAChR. Despite this remarkable sensitivity, exogenous ACh readily stimulated the mAChR in the intact posterior SCC preparation but failed to activate RDMPP unless the acetylcholinesterase inhibitor physostigmine was present, or high concentrations of ACh were used (>3 mM). In frog, RDMPP most likely underlies the rapid excitatory response seen during efferent stimulation.

Animals↗
PubMed1990

Cholinergically-induced changes in outward currents in hair cells isolated from the semicircular canal of the frog.

Two cholinergically-induced modulations of membrane conductances have been identified in hair cells isolated from the crista ampullaris of the leopard frog (Rana pipiens), using the whole cell recording configuration of the patch clamp technique. Of 56 crista hair cells tested, 28 showed drug-induced changes in membrane current or membrane potential which were repeatable and could be reversed with washout of drug. The predominant effect (observed in 20 hair cells) of acetylcholine (Ach, 100 microM) to 1mM) or carbachol (1 microM to 50 microM) applied to these hair cells was the reduction of an outward current corresponding to a change in conductance of approximately -0.22 nS. This action by Ach on hair cells has been inferred from previous studies of afferent fiber discharge which reported an increase in firing rate with stimulation of efferent fibers or exogenous application of cholinomimetics (Bernard et al., 1985; Valli et al., 1986; Guth et al., 1986; Norris et al., 1988a). The Ach-induced reduction in outward current was associated with a depolarization of the zero-current membrane potential by approximately +2.5 mV. In a total of 8 hair cells, an Ach-induced reversible increase in outward current was recorded. Changes in conductance were approximately +0.13 nS and were associated with a hyperpolarization of the zero-current membrane potential by approximately -2.2 mV. This current increase is likely to be responsible for the inhibitory post-synaptic potentials (IPSPs) which have previously been recorded intracellularly from acoustico-lateralis hair cells during stimulation of the efferent innervation (Flock and Russell, 1976; Ashmore and Russell, 1982; Art et al., 1984, 1985). Of the remaining 28 hair cells, six cells failed to exhibit any change in membrane conductance or membrane potential in the presence of cholinomimetics while an additional 15 cells exhibited decreases, and 7 cells exhibited increases in outward conductance, during application of Ach or carbachol, which were neither reversible with washout nor repeatable. The Ach-induced decrease in outward current could be reversible blocked by removal of Ca2+ from the external solution. The antagonism of the Ach-induced decrease in outward current by atropine (10(-5) M) suggests that this current may correspond to a facilitatory, 'atropine-preferring' Ach receptor mediated response previously identified in the isolated semicircular canal (Norris et al., 1988a).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed2006

Absent semicircular canals in CHARGE syndrome: radiologic spectrum of findings.

BACKGROUND AND PURPOSE: This paper describes the CT findings that characterize the middle and inner ear anomalies in coloboma, heart defects, choanal atresia, mental retardation, genitourinary, and ear anomalies (CHARGE) syndrome. With this information, neuroradiologists will be better prepared to provide clinically relevant information to their referring physicians regarding this rare syndrome. MATERIALS AND METHODS: CT studies from 13 patients were reviewed by 2 neuroradiologists with Certificate of Additional Qualification. Each ear was counted separately for a total of 26 ears. Middle and inner ear anomalies associated with CHARGE syndrome were categorized. Investigational review board approval was obtained. RESULTS: Twenty of 26 (77%) ears demonstrated cochlear aperture atresia. Four of these ears were evaluated with MR imaging and were found to lack a cochlear nerve. Twenty-one of 26 (81%) cochlea had some form of dysplasia. Six of 26 (23%) round windows were aplastic. Three of 26 (12%) round windows were hypoplastic. Twenty-one of 26 (81%) oval windows were atretic or aplastic. Fifteen of 26 (58%) vestibules were hypoplastic or dysplastic. There were 5 of 26 (19%) enlarged vestibular aqueducts. Twelve of 26 (46%) vestibular aqueducts had an anomalous course. All cases demonstrated absent semicircular canals. Twenty-three of 26 (88%) facial nerve canals had an anomalous course. Four of 26 (15%) tympanic segments were prolapsed. Three of 26 (12%) temporal bones had an anomalous emissary vein referred to as a petrosquamosal sinus. Twenty-one of 26 (81%) middle ear cavities were small. Twenty-three of 26 (93%) ossicles were dysplastic with ankylosis. Three of 26 (12%) internal auditory canals were small. CONCLUSION: The CT findings that correlate to the anomalies of CHARGE syndrome affect conductive as well as sensorineural hearing. Stenosis of the aperture for the cochlear nerve aperture on CT is suggestive of hypoplasia or absence of the cochlear nerve, which has been demonstrated in some cases by MR. Absence of the cochlear nerve would be a contraindication to cochlear implantation.

Abnormalities, Multiple↗
PubMed1998

Otolith and semicircular canal contributions to the human binocular response to roll oscillation.

Three normal human subjects were oscillated about their naso-occipital axis in a supine position at 0.4 Hz and 0.1 Hz, both in darkness and in the light with a structured fixation target. The same subjects were oscillated in roll about an upright position, at the same frequencies, in darkness; and also about axes directed 20 degrees and 40 degrees to the left and to the right of the midsagittal plane, at 0.4 Hz, in darkness. Three-dimensional binocular eye movements were recorded using video-oculography. All stimuli induced a predominantly torsional nystagmus with small disconjugate head-vertical (skew) and conjugate head-horizontal components. For roll oscillation, the torsional slow phase velocity gain was higher in the light and generally increased with the stimulation frequency. In darkness, only one subject had significantly higher torsional gains in the upright compared to the supine position (12% difference), suggesting that the otolith contribution to the roll response is minimal at the frequencies tested. The slow phase velocity gain of the skew increased with fixation in two subjects. but decreased in the third subject; these changes were related to changes in eye vergence. In the upright position, with oblique axes of rotation, the head-vertical eye movements were asymmetrical, with the outermost eye executing a larger amplitude movement. The disconjugate head-vertical eye movements observed can be explained by the pattern of vertical semicircular canal stimulation and their connections to the extraocular muscles. In humans, skewing of the eyes may compensate for the eccentricity of the foveae which lie in the temporal retina and undergo vertical translations in opposite directions when the eyes tort.

Adult↗