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PubMed1999

Effects of epinephrine on ouabain-sensitive, K(+) -dependent P-nitrophenylphosphatase activity in strial marginal cells of guinea pigs.

In strial marginal cells, Na+/K(+)-ATPase activity is abundant, and contributes to maintain the characteristic electrolyte composition of the cochlear endolymph. In the present study, to clarify the relationship between epinephrine and strial Na+/K(+)-ATPase activity, the ouabain-sensitive, K+-dependent p-nitrophenylphosphatase (K(+)-NPPase) activity of strial marginal cells was investigated with a cerium-based method in normal guinea pigs and guinea pigs treated with reserpine, epinephrine, and reserpine plus epinephrine. In our previous study, K(+)-NPPase activity had almost completely decreased 3 to 20 days after reserpine administration. In the present study, at 10 days after reserpinization and following repeated epinephrine treatment, enzyme activity was detectable. These results suggest that exogenous epinephrine was able to restore strial K(+)-NPPase activity in the reserpine-treated animals, and that epinephrine might increase strial Na+/K(+)-ATPase activity.

4-Nitrophenylphosphatase↗

PubMed1992

The canalith repositioning procedure: for treatment of benign paroxysmal positional vertigo.

The Canalith Repositioning Procedure (CRP) is designed to treat benign paroxysmal positional vertigo (BPPV) through induced out-migration of free-moving pathological densities in the endolymph of a semicircular canal, using timed head maneuvers and applied vibration. This article describes the procedure and its rationale, and reports the results in 30 patients who exhibited the classic nystagmus of BPPV with Hallpike maneuvers. CRP obtained timely resolution of the nystagmus and positional vertigo in 100%. Of these, 10% continued to have atypical symptoms, suggesting concomitant pathology; 30% experienced one or more recurrences, but responded well to retreatment with CRP. These results also support an alternative theory that the densities that impart gravity-sensitivity to a semicircular canal in BPPV are free in the canal, rather than attached to the cupula. CRP offers significant advantages over invasive and other noninvasive treatment modalities in current use.

Adult↗

PubMed2004

Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model.

BACKGROUND: Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin. We investigated the relationship between pendrin and deafness using mice that have (Slc26a4+/+) or lack a complete Slc26a4 gene (Slc26a4-/-). METHODS: Expression of pendrin and other proteins was determined by confocal immunocytochemistry. Expression of mRNA was determined by quantitative RT-PCR. The endocochlear potential and the endolymphatic K+ concentration were measured with double-barreled microelectrodes. Currents generated by the stria marginal cells were recorded with a vibrating probe. Tissue masses were evaluated by morphometric distance measurements and pigmentation was quantified by densitometry. RESULTS: Pendrin was found in the cochlea in apical membranes of spiral prominence cells and spindle-shaped cells of stria vascularis, in outer sulcus and root cells. Endolymph volume in Slc26a4-/- mice was increased and tissue masses in areas normally occupied by type I and II fibrocytes were reduced. Slc26a4-/- mice lacked the endocochlear potential, which is generated across the basal cell barrier by the K+ channel KCNJ10 localized in intermediate cells. Stria vascularis was hyperpigmented, suggesting unalleviated free radical damage. The basal cell barrier appeared intact; intermediate cells and KCNJ10 mRNA were present but KCNJ10 protein was absent. Endolymphatic K+ concentrations were normal and membrane proteins necessary for K+ secretion were present, including the K+ channel KCNQ1 and KCNE1, Na+/2Cl-/K+ cotransporter SLC12A2 and the gap junction GJB2. CONCLUSIONS: These observations demonstrate that pendrin dysfunction leads to a loss of KCNJ10 protein expression and a loss of the endocochlear potential, which may be the direct cause of deafness in Pendred syndrome.

Animals↗

PubMed2004

Effect of gravity on the caloric stimulation of the inner ear.

Robert Barany won the 1914 Nobel Prize in medicine for his convection hypothesis for caloric stimulation. Microgravity caloric tests aboard the 1983 SpaceLab 1 mission produced nystagmus results that contradicted the basic premise of Barany's convection theory. In this paper, we present a fluid structural analysis of the caloric stimulation of the lateral semicircular canal. Direct numerical simulations indicate that on earth, natural convection is the dominant mechanism for endolymphatic flow. However, in the microgravity environment of orbiting spacecraft, where buoyancy effects are mitigated, an expansive convection becomes the sole mechanism for producing endolymph motion and cupular displacement. Transient 1 g and microgravity case studies are presented to delineate the different dynamic behaviors of the 1 g and microgravity endolymphatic flows. The associated fluid-structural interactions are also analyzed based on the time evolution of cupular displacements.

Biophysical Phenomena↗

PubMed2006

Soluble megalin is accumulated in the lumen of the rat endolymphatic sac.

The endolymphatic sac (ES) is believed to play an important role in maintaining homeostasis in the inner ear by the absorption and endocytosis of endolymph. Megalin is a 600-kDa multiligand endocytic receptor expressed in certain types of absorptive epithelia including kidney proximal tubules. We analyzed the immunoreactivity for megalin in rat ES by immunofluorescence, immunogold electron microscopy, and immunoblotting. With immunostaining, the luminal substances of the ES were strongly stained for megalin. Megalin was also localized in luminal macrophage-like cells and both types of epithelial cell (mitochondria-rich cells and ribosome-rich cells). In these cells, the megalin was localized in the lumen of endosomes, but was not membrane associated. This localization pattern indicates that the megalin in these cells is not a membrane receptor, but merely one of the constituents that are endocytosed from the lumen of the ES. Immunoblotting indicated that the megalin in the ES is a 210-kDa molecule lacking a cytoplasmic domain. This suggests that the megalin in the ES may be a soluble form, different from the 600-kDa membrane-bound receptor expressed in kidneys. Taken together, it is likely that the megalin in the ES lumen is a soluble component and may be endocytosed by the ES epithelial cells. Furthermore, we found that the tectorial membrane, an acellular structure in the cochlea, gave a strong megalin immunoreaction. Since the cochlea is connected to the ES, the megalin may be transported alone or with the components of the tectorial membrane from the cochlea to the ES lumen through longitudinal flow.

Animals↗

PubMed1982

Intracochlear microprobe analysis.

Energy dispersive x-ray analysis (EDXA) or "microprobe analysis" provides cochlear physiologists with a means of accurately assessing relative ionic concentrations in selected portions of the auditory mechanism. Rapid freezing followed by lyophilization allows the recovery of fluid samples in crystalline form not only from perilymphatic and endolymphatic spaces, but also from much smaller subregions of the cochlea. Because samples are examined in a solid state, there is no risk of diffusion into surrounding or juxtaposed fluids. Samples of cochlear tissues may also be evaluated without the danger of intercellular ionic diffusion. During direct visualization by scanning electron microscopy, determination of the biochemical makeup of the material being examined can be simultaneously, assuring the source of the data collected. Other potential advantages and disadvantages of EDXA are reviewed. Initial findings as they relate to endolymph, perilymph, stria vascularis, and the undersurface of the tectorial membrane are presented.

Cochlea↗

PubMed1985

Furosemide ototoxicity: clinical and experimental aspects.

Furosemide is an ototoxic diuretic. Furosemide injection is followed by a rapid, but reversible decrease of the endocochlear potential and eighth nerve action potential with a more gradual decrease of the endolymph potassium concentration. In contrast to the reversible effects of furosemide alone on the cochlea, the combination of kanamycin with furosemide resulted in irreversible changes in cochlear function which were associated with elevated levels of kanamycin in the blood and perilymph of the experimental animals. There was a striking similarity between the blood level measured by high pressure liquid chromatography at the time of recovery of auditory function in experimental animals and the ototoxic blood levels proposed by others in clinical literature. These findings help to provide a pharmacologic basis for the clinical observation of furosemide-induced hearing loss.

Animals↗

PubMed1990

Size variations in the lateral intercellular spaces of the endolymphatic sac induced by dietary factors.

Since much evidence suggests that the endolymphatic sac is responsible for endolymph resorption, and that the endolymphatic sac lateral intercellular spaces which are lined by the energy-dependent transport complex NA+,K(+)-ATPase are important in this process, we sought to evaluate the effects of dietary salt and a food extract that inhibits the activity of Na+,K(+)-ATPase on lateral intercellular space size. Animals fed this food factor and a high-sodium diet had significantly smaller endolymphatic sac lateral intercellular spaces than those animals fed only a high-sodium diet (analysis of variance with Scheffe's multiple comparison test, P less than 0.001). Animals fed a high-sodium diet had significantly larger endolymphatic sac lateral intercellular spaces than those animals fed a control diet only (analysis of variance with Scheffe's multiple comparison test, P less than 0.001). Results of this study suggest that dietary sodium affects endolymphatic sac fluid dynamics and that other food factors may regulate sodium metabolism, and therefore endolymphatic sac function.

Animals↗

PubMed1994

Particle repositioning maneuver for benign paroxysmal positional vertigo.

The recent demonstration of free-floating particles in the endolymph of the posterior semicircular canal in patients with benign paroxysmal positional vertigo (BPPV) has renewed interest in the physiology and treatment of this entity. The particle repositioning maneuver (PRM) relocates the free-floating particles from the posterior semicircular canal back into the utricle, relieving the patient of bothersome, often long-standing vertigo. This report represents a prospective study of 27 consecutive patients seen with a diagnosis of BPPV. Eighty-four percent of the patients treated with the particle repositioning maneuver who had no other associated pathology were cured or significantly improved with this new technique. Two patients who failed conservative management went on to surgical intervention with the posterior semicircular canal occlusion. The authors find the particle repositioning maneuver effective for many patients with benign positional vertigo and recommend it as the first-line treatment modality for BPPV.

Adult↗

PubMed1995

Effects of endolymphatic duct occlusion on the structure and function of the endolymphatic sac in the adult guinea pig.

The endolymphatic sac (ELS) has been shown to respond rapidly to sudden disruptions in fluid balance such as labyrinthectomy or systemic administration of hyperosmolar agents. The present study was designed to determine the ELS response to slower changes in fluid dynamics by occluding the endolymphatic duct (ELD), thereby interrupting the longitudinal flow of endolymph to the ELS. Morphologic studies and autoradiographic techniques were used to evaluate the effects of ELD obstruction on the structure and function of the ELS after 48 hours. There were no significant changes in cellular morphology and a slight decrease in the incorporation of radiolabeled glucose when compared with normal ELS cells. We conclude that it is rapid change in fluid balance that triggers the ELS response, which is not seen with disruption of longitudinal flow.

Animals↗

PubMed2006

Effects of CO2/HCO3- in perilymph on the endocochlear potential in guinea pigs.

The effect of CO(2)/HCO(3)(-) on the endocochlear potential (EP) was examined by using both ion-selective and conventional microelectrodes and the endolymphatic or perilymphatic perfusion technique. The main findings were as follows: (i) A decrease in the EP from approximately +75 to approximately +35 mV was produced by perilymphatic perfusion with CO(2)/HCO(3)(-)-free solution, which decrease was accompanied by an increase in the endolymphatic pH (DeltapH(e), approximately 0.4). (ii) Perilymphatic perfusion with a solution containing 20 mM NH(4)Cl produced a decrease in the EP (DeltaEP, approximately 20 mV) with an increase in the pH(e) (DeltapH(e), approximately 0.2), whereas switching the perfusion solution from the NH(4)Cl solution to a 5% CO(2)/25 mM HCO(3)(-) solution produced a gradual increase in the EP to the control level with the concomitant recovery of the pH(e). (iii) The perfusion with a solution of high or low HCO(3)(-) with a constant CO(2) level within 10 min produced no significant changes in the EP. (iv) Perfusion of the perilymph with 10 microg/ml nifedipine suppressed the transient asphyxia-induced decrease in EP slightly, but not significantly. (v) By contrast, the administration of 1 microg/ml nifedipine via the endolymph inhibited significantly the reduction in the EP induced by transient asphyxia or perilymphatic perfusion with CO(2)/HCO(3)(-)-free or 20 mM NH(4)Cl solution. These findings suggest that the effect of CO(2) removal from perilymphatic perfusion solution on the EP may be mediated by an increase in cytosolic Ca(2+) concentration induced by an elevation of cytosolic pH in endolymphatic surface cells.

Ammonium Chloride↗

PubMed2001

Passage of dextran magnetite nanoparticles through the subcupular space of the pigeon.

We examined the permeability of the subcupular space for endolymph flow in the pigeon. A new technique was developed in which nanoparticles consisting of dextran magnetite were attracted by use of a magnet, instead of injecting a dye solution. The method was revealed to prevent an excess pressure application by the injection of dye solution. The Berlin blue color resulting from the dextran magnetite nanoparticles was found mainly within the subcupular space contacting with the sensory hairs. Further formation of the Berlin blue was found within the sensory cells. The result supports the idea that the fluid passes through the subcupular space.

Animals↗

PubMedDate not supplied

Analysis of curves Na-24 efflux from membrane labyrinth containing stria vascularis.

The efflux of Na-24 was investigated in isolated labyrinths from a membrane section containing stria vascularis and spiral ligament in artificial endolymph medium. The efflux curves were calculated and compartmental analyses were made. The theoretical possibility of a exchange of sodium between compartments connected in different ways was considered. The calculated values of rate constant of transmembranal sodium fluxes are 0.0282+/-0.0052 min-1 and the half-time of the exchange of sodium between intracellular compartments is 24.27+/-4.53 min. The distribution of sodium in tissue with a commonly applied simplification gives 90% Na+ in the extracellular compartment and 3% Na+ in the intracellular compartment of the total tissue sodium content. The possibility of measuring the rate constant of transmembranal electrolyte fluxes in this tissue seems encouraging for future investigation of the mechanism by which they are transported.

Animals↗

PubMed1975

Experimental aural barotrauma. Electrophysiological and morphological findings.

The electrophysiological findings show a time and pressure related decrease in function of the CM and the N1 potentials. Sudden changes were correlated with tympanic membrane perforations. Some of the decreased function is accounted for by middle ear effusion and hemorrhages, reducing mechanically the transmission of sound energy through the middle ear. This was evidenced by an improvement of function when the fluids were removed. Remaining decreases in function were interpreted as a result of influences on the inner ear function or of undisclosed middle ear changes. No differences were noted in cochlear function between animals subjected to sustained or intermittent middle ear pressures. Neither were any morphological differences noted between these two groups in the middle or inner ear. The morphological middle ear findings correlated well with previous clinically and experimentally induced changes with increased/decreased middle ear pressure. The cochlear findings include the interesting observation of an intact round window membrane, a clear endolymph, and a normal Organ of Corti in all cases. Positive findings were a high frequency of hemorrhage, most commonly demonstrated in the scala tympani of the basal turn close to the round window. The origin of the hemorrhages could not be demonstrated with the present investigation. The hemorrhages often appeared to be related to the cochlear aqueduct. The occurrence of hemorrhage was clearly related to increased negative pressure, and the non-existence of hemorrhage was always related to either tympanic membrane perforations or low applied pressure. Further frequent findings were distention, collapse, and rupture of the inner ear membranes which must be interpreted with great circumspection due to the method used. Likewise, some of the pathological cochlear findings may be due to pathological conditions which are not necessarily related to induced middle ear pressure.

Acoustic Stimulation↗

PubMedDate not supplied

Aminotransferases in post-mortem cochlear fluids.

Aspartate and alanine aminotransferase (ASAT, ALAT) activities were measured in human post-mortem sera, cerebrospinal fluid (CSF), perilymph and endolymph. Due to heart and/or liver morbidity during a terminal illness, the ASAT and ALAT serum activities were considerably increased as compared with normal and both were 20--30 times higher (p less than 0.001) than in CSF or inner ear fluids. CSF and inner ear fluids showed mutually similar values.

Alanine Transaminase↗

PubMedDate not supplied

Intermediate endocochlear potential levels induced by hypoxia.

It seems that the positive potential of the scala media (endocochlear potential [EP]) and the high potassium concentration in the endolymph are generated and maintained by an electrogenic pump. In order to study its properties, the EP was measured in cats ventilated with low oxygen gas mixtures (2.25-10%). It was found that the EP could be maintained at intermediate levels which were more or less linear functions of blood oxygen tension (25-60 mmHg), showing that the pump can operate on intermediate levels. This hypoxic preparation may contribute to the study of cochlear blood flow.

Acoustic Stimulation↗

PubMedDate not supplied

Electron probe determination of relative ion distribution in the inner ear.

The relative amounts of potassium and chlorine present in various parts of the inner ear were studied by using an energy dispersive X-ray spectrometer in conjunction with a scanning electron microscope. Whereas the amount of chlorine was high in all compartments investigated, potassium was high in endolymphatic spaces and low in perilymphatic spaces. High contents of potassium and chlorine were also found in the tectorial membrane, in the inner sulcus and in the cupula of the semicircular canal. It is concluded that the tectorial membrane and the cupula do not present a barrier to ions and that therefore the sensory hairs in the inner ear are exposed to the ionic environment provided by the endolymph.

Animals↗

PubMedDate not supplied

Experimentally (atoxyl) induced ampullar degeneration and damage to the maculae utriculi.

Atoxyl administration to guinea pigs may cause vesicular degeneration of both the secretory and the sensory regions of the cristae ampullares and macula utriculi. Some of the severely damaged secretory cells were even expelled from the surface into the endolymphatic space. The nerve chalices of type I hair cells disintegrated. The degeneration of the secretory region will thus block the endolymph circulation and the electrolyte balance is likely to collapse. Whether hair cell degeneration can best be explained on this basis (indirect atoxyl effect) or by a direct action of atoxyl on the hair cells and the nerve chalices of type I hair cells is discussed.

Aniline Compounds↗