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At least 127 records · Page 7Linked to original sources

How endolymph pressure modulates semicircular canal primary afferent discharge.

Histological observation of endolymphatic hydrops in subjects suffering from Meniere's disease/syndrome and the presence of vestibular symptoms in experimentally induced endolymphatic hydrops have led to considerable debate regarding the potential role of inner-ear pressure. Could a condition influencing endolymphatic volume regulation lead to transient changes in translabyrinthine pressure sufficiently large to alter primary afferent discharge rates? To investigate this question we built a highly sensitive laser-based pressure sensor and recorded endolymphatic pressure modulations within the horizontal semicircular canal ampulla in response to mechanical stimuli for simple head rotation and controlled volume injection. The most sensitive primary afferents responded to changes in endolymph pressures as low as 0.005 Pa (re: perilymph)--a pressure considerably lower than that observed in most experimentally induced hydropic conditions. This threshold pressure was generated by a approximately 25 picoliter volume injection stimulus. Semicircular canal afferent responses to endolymphatic pressure can be explained on the basis of pressure-induced hydrops, which causes dilation of the ampulla, deformation of the cupula, hair bundle movement, and afferent discharge. Primary afferent responses to maintained stimuli were transient in nature and recovered to pre-stimulus background discharge rates following a period of adaptation. Results demonstrate that the semicircular canals are indeed sensitive to small changes in translabyrinthine pressure in addition to head-movement-related changes in transcupular pressure.

Animals↗

Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion.

The kinetics of gentamicin in the inner ear fluids of rats were studied up to 15 days after cessation of a 2-day constant infusion of 10 micrograms/min. In endolymph, the concentration of gentamicin persisted at about 1 microgram/ml for up to 15 days, precluding the determination of the half-life of the drug in this fluid. In perilymph, gentamicin cleared more slowly than after a shorter period of infusion. These results suggest that the tissues of the inner ear could bind the aminoglycoside and then slowly release it into the surrounding fluids.

Animals↗

Electrochemical heterogeneity of the cochlear endolymph: effect of acetazolamide.

The electrochemical composition of endolymph (EL) of two adjacent cochlear turns was studied in anesthetized rats. Differences in [K]EL, [Cl]EL, and endocochlear potential (EP) were found between the basal turn (165.6 +/- 3.0 mM, n = 14; 144.6 +/- 2.1 mM, n = 14;96.6 +/- 1.9 mV, n = 5, respectively) and the middle turn (155.7 +/- 2.5 mM, n = 15; 133.2 +/- 1.5 mM, n = 15; 87.0 +/- 1.6 mV, n = 6, respectively). The pH values of inner ear fluids were evaluated with 5,5-dimethyloxazolidine-2,4-dione: EL pH of either turn was not different from blood and perilymph (PL) pH. Acetazolamide (40 mg X kg body wt-1) reduced EP and [Cl]EL at each turn by about 20 and 6%, respectively, but [K]EL was unchanged. The electrochemical differences between the two turns persisted. Acetazolamide produced a 0.2-unit decrease in blood pH while the pH values of EL and PL remained unchanged. These results suggest the existence of an electrochemical gradient within EL from the base to the apex of the cochlea involving K+ and Cl- concentrations. H+ and HCO-3 do not appear to participate in this gradient, and the acid-base status in EL could be maintained both by active H+ transport into EL and by HCO-3 formation in the cochlear epithelium.

Acetazolamide↗

Endolymph formation in the inner ear of pigeons.

The endolymphatic space of pigeons was studied by using double-barrelled electrodes with a potassium liquid ion exchanger. The K+ activity of the endolymph was 155 mM in the cochlea and 133 mM in the ampulla, respectively. Positive DC potential in the cochlea (+14.5 mV) was much lower than in guinea pigs (+80 mV) whereas in the ampulla of pigeons the DC potential (+7.4 mV) was 2 times higher than that of guinea pigs (+3.9 mV). General application of ethacrynic acid in pigeons induced a weak change in DC potential and no typical intercellular edema in the cochlea and ampulla. Local application of ethacrynic acid and ouabain in the cochlea and ampulla of pigeons induced a negative DC potential of between -30 and -40 mV. This negative DC potential was higher than the anoxia-induced negative potential. Short hypoxia during a drug-induced DC potential resulted in a decrease in DC potential above the diffusion potential. Below the diffusion potential additional hypoxia increased the DC potential independent of the cause of intoxication.

Animals↗

Hydrostatic pressure measurements of endolymph and perilymph in a guinea pig model of endolymphatic hydrops.

The primary histologic correlate of Menière's disease is endolymphatic hydrops. From this, many investigators have postulated the existence of endolymphatic hypertension, although there have been no measurements published to substantiate this concept. Seventy guinea pigs, surgically treated with right endolymphatic duct obstruction, were later assessed by use of a micro-electrode technique that measured their endolabyrinthine hydrostatic pressures. For 21 of these animals, the pressures of both scala tympani (Pst) and scala media (Psm) of both ears of each animal were successfully measured. Similar measurements were made in a control group of 25 guinea pigs that had not undergone any previous surgery. For normal ears--as well as those with hydrops-pressure differences between perilymph and endolymph (Psm - Pst) varied around 0 +/- 2.0 mm Hg. When only the right (obstructed) ears were considered, there appeared to be a slight, relative pressure elevation (p less than 0.05) in scala media during the first 7 days after endolymphatic duct obstruction-and in those ears with EP, less than 70 mV. The magnitude of this pressure difference that can be attributed to the state of endolymphatic hydrops-and not to natural variability-is calculated (within 95% confidence limits) to be less than 0.5 mm Hg.

Animals↗

Endolymph pressure in Menière's disease.

During the streptomycin perfusion/shunt of the lateral semicircular duct operation for Meniere's disease, the lateral semicircular duct is exposed by removal of the bone of the lateral semicircular canal. Before perfusion with streptomycin and creation of a shunt in the lateral semicircular duct, the pressure in the lateral semicircular duct is measured while electrocochleography is being recorded. In most ears with Meniere's disease, the pressure necessary to indent the lateral semicircular duct is 2 to 3 mm of water. The pressure is more in those ears with a large negative summating potential than in those with a normal negative summating potential. The pressure is less after the shunt in the lateral semicircular duct is created and the negative summating potential returns to normal. In some ears with the classic picture of Meniere's disease, the endolymph pressure is normal and there is a normal negative summating potential. Presumably, one should not create a shunt in the lateral semicircular duct in ears with normal pressure.

Audiometry, Evoked Response↗

Steady-state adaptation of mechanotransduction modulates the resting potential of auditory hair cells, providing an assay for endolymph [Ca2+].

The auditory hair cell resting potential is critical for proper translation of acoustic signals to the CNS, because it determines their filtering properties, their ability to respond to stimuli of both polarities, and, because the hair cell drives afferent firing rates, the resting potential dictates spontaneous transmitter release. In turtle auditory hair cells, the filtering properties are established by the interactions between BK calcium-activated potassium channels and an L-type calcium channel (electrical resonance). However, both theoretical and in vitro recordings indicate that a third conductance is required to set the resting potential to a point on the I(Ca) and I(BK) activation curves in which filtering is optimized like that found in vivo. Present data elucidate a novel mechanism, likely universal among hair cells, in which mechanoelectric transduction (MET) and its calcium-dependent adaptation provide the depolarizing current to establish the hair cell resting potential. First, mechanical block of the MET current hyperpolarized the membrane potential, resulting in broadband asymmetrical resonance. Second, altering steady-state adaptation by altering the [Ca2+] bathing the hair bundle changed the MET current at rest, the magnitude of which resulted in membrane potential changes that encompassed the best resonant voltage. The Ca2+ sensitivity of adaptation allowed for the first physiological estimate of endolymphatic Ca2+ near the MET channel (56 +/- 11 microM), a value similar to bulk endolymph levels. These effects of MET current on resting potential were independently confirmed using a theoretical model of electrical resonance that included the steady-state MET conductance.

Adaptation, Physiological↗

Asphyxia and diuretic-induced changes in the Ca2+ concentration of endolymph.

Using Ca2+ -selective microelectrodes based on the neutral carrier, ETH-1001 with polyvinyl chloride (PVC), we have measured changes in the free Ca2+ concentration of guinea pig cochlear endolymph ([Ca](e)) after transient asphyxia or intravenous administration of diuretics. Under the control conditions, the endocochlear potential (EP) was +80 mV, and the [Ca](e) was in the range 1.4 x 10(-7)-2.4 x 10(-6) M (n = 16). Transient asphyxia (1-1.5 min) produced an increase in the [Ca](e) with a fall in the EP, whereas the cessation of the asphyxia led to a quick recovery of both [Ca](e) and EP to their control levels. Intravenous administration of furosemide (60 mg/kg) or bumetanide (30 mg/kg) also caused an increase in the [Ca](e) with a fall in the EP, followed by a gradual recovery of both [Ca](e) and EP. From these results, we obtained a significant correlation between EP and p[Ca](e) (= -log[Ca](e)), and conclude that (1) the [Ca](e) is extremely low, around 10(-6) M or less, under normal conditions and (2) the [Ca](e) is directly correlated with EP under physiological conditions.

Animals↗

Ionic composition of the endolymph and sensory transduction in labyrinthine organs.

The role of various ions in stimuli conversion has been investigated in isolated frog semicircular canals, by replacing the endolymph with solutions deprived in turn of Na+, K+, Cl- and Ca++. Mechanical and electrical stimuli were employed and slow ampullar and nerve potentials were recorded, together with the afferent discharge of impulses in the eighth nerve. The results support evidence that K+ is the carrier of the receptor current, as postulated in Davis' hypothesis, while Ca++ is essential in the processes which allow the current to be modulated during cupula deflections and therefore endon hair cells with mechanical sensitivity.

Acoustic Stimulation↗

A survey of the effects of loop diuretics on the zonulae occludentes of the perilymph-endolymph barrier by freeze fracture.

The acute (30 min) effects of the loop diuretics piretanide, ethacrynic acid, bumetanide, furosemide, and azosemide, and the chronic (8 days) effects of furosemide and bumetanide on the zonulae occludentes (tight junctions) of the perilymph-endolymph barrier in the stria vascularis and in Reissner's membrane of the basal cochlear turns were studied by freeze-fracture. Quantitative analysis of their effects indicated that the structural integrity of the barrier was modified by either as increase or a decrease in the number, depth, and density of the strands of the tight junctions of the strial marginal cells. Only azosemide appeared to modify the tight junctions between the epithelial cells of Reissner's membrane, but it had little effect on the strial junctions. The tight junctions between the basal cells of the stria appeared to be the least affected by the various loop diuretics, although piretanide appeared to increase randomly the intercellular spaces lying between the strands.

Animals↗

Fluid kinetics of endolymph during calorization.

Various theories on the mechanism of caloric vestibular excitability are discussed and compared with our model, which involves two factors of endolymph movement: thermoconvection and fluid expansion. With this theory, caloric nystagmus in microgravity can be explained, as well as certain phenomena on earth, such as different vestibular responses depending on body position.

Endolymph↗

[Mathematic model of the cupuloendolymphatic system for various densities of cupula and endolymph].

This paper presents a mathematical model of time-course variations of the cupulo-endolymphatic system which can be described by the Steinhauzen phenomenological equation for the case of a unidimensional toroid, assuming that the densities of the cupula and endolymph are identical. If the densities are different, the time-course variations of the cupuloendolymphatic system may aggravate and manifest at the powered stages of space flight.

Acceleration↗

[The changes of Ca++ concentrations of endolymph and perilymph of the experimental endolymphatic hydrops].

The changes of Ca++ concentrations of endo- and perilymph were determined by using atomic absorption spectrophotometry in the guinea pig model which endolymphatic sac and duct were surgically obliterated one month ago. The results showed that the Ca++ concentrations of endolymph of hydropic ear was 0.181+0.129 mmol/L (n = 9), and that of the control group was 0.020+0.014 mmol/L (n = 10). The paired t test (P < 0.01) showed significant difference. In perilymph, the concentrations of Ca++ of hydropic ear was 0.679+0.340 mmol/L (n = 10), and that of the control ears was 0.730+0.385 mmol/L (n = 10). The paired t-test (P > 0.05) showed no significant difference. The principle of the increase of Ca++ concentrations in the endolymphatic hydrops was also discussed.

Animals↗

The nature of the ototoxic actions of ethacrynic acid upon the mammalian endolymph system. II. Structural-functional correlates in the stria vascularis.

The relationship of the ultrastructural changes in the stria vascularis to the functional alterations in the endolymph system was investigated in 23 rats at various times up to 120 min after a single intravenous injection of ethacrynic acid (60 mg kg-1). The overall effect upon the marginal cells, revealed by the development and regression of marked cytoplasmic swelling, was reasonably well correlated with the derangements produced in the strial ion-transporting mechanisms. The pathophysiological relationships of the action upon the intermediate cells was less exact and no unequivocal structural correlates were found for the diminution in membrane permeability and the probable late decrease in energy production. The size of the interstitial spaces was determined mainly by the variations in volume of the marginal and intermediate cells.

Animals↗