Changes In Endocochlear Potential Research Articles

Glial-Specific Deletion of Med12 Results in Rapid Hearing Loss via Degradation of the Stria Vascularis.

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiologic analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies reveal that Med12 regulates auditory function in the adult by preserving the structural integrity of the stria vascularis.SIGNIFICANCE STATEMENT Mutations in Mediator protein complex subunit 12 (Med12) are associated with X-linked intellectual disability syndromes and hearing loss. Using temporal-conditional genetic approaches in CNS glia, we found that loss of Med12 results in severe hearing loss in adult animals through rapid degeneration of the stria vascularis. Our study describes the first animal model that recapitulates hearing loss identified in Med12-related disorders and provides a new system in which to examine the underlying cellular and molecular mechanisms of Med12 function in the adult nervous system.

Recovery of endocochlear potential after severe damage to lateral wall fibrocytes following acute cochlear energy failure.

Reduction of endocochlear potential (EP) is one of the main causes of sensorineural hearing loss. In this study, we investigated changes in the EP using a mouse model of acute cochlear energy failure, which comprised severe cochlear lateral wall damage induced by the local administration of 3-nitropropionic acid to the inner ear. We also analyzed the correlation between EP changes and histological findings in the cochlear lateral wall. We detected the recovery of the EP and hearing function at lower frequencies after severe damage of the cochlear lateral wall fibrocytes at the corresponding region. Remodeling of the cochlear lateral wall was associated with EP recovery, including the re-expression of ion transporters or gap junctions (i.e. Na/K/ATPase-β1 and connexin 26). These results indicate a mechanism for late-phase hearing recovery after severe deafness, which is frequently observed in clinical settings.

Systemic lipopolysaccharide induces cochlear inflammation and exacerbates the synergistic ototoxicity of kanamycin and furosemide.

Aminoglycoside antibiotics are highly effective agents against gram-negative bacterial infections, but they cause adverse effects on hearing and balance dysfunction as a result of toxicity to hair cells of the cochlea and vestibular organs. While ototoxicity has been comprehensively studied, the contributions of the immune system, which controls the host response to infection, have not been studied in antibiotic ototoxicity. Recently, it has been shown that an inflammatory response is induced by hair cell injury. In this study, we found that lipopolysaccharide (LPS), an important component of bacterial endotoxin, when given in combination with kanamycin and furosemide, augmented the inflammatory response to hair cell injury and exacerbated hearing loss and hair cell injury. LPS injected into the peritoneum of experimental mice induced a brisk cochlear inflammatory response with recruitment of mononuclear phagocytes into the spiral ligament, even in the absence of ototoxic agents. While LPS alone did not affect hearing, animals that received LPS prior to ototoxic agents had worse hearing loss compared to those that did not receive LPS pretreatment. The poorer hearing outcome in LPS-treated mice did not correlate to changes in endocochlear potential. However, LPS-treated mice demonstrated an increased number of CCR2(+) inflammatory monocytes in the inner ear when compared with mice treated with ototoxic agents alone. We conclude that LPS and its associated inflammatory response are harmful to the inner ear when coupled with ototoxic medications and that the immune system may contribute to the final hearing outcome in subjects treated with ototoxic agents.

Change in Endocochlear Potential During Experimental Insertion of a Simulated Cochlear Implant Electrode in the Guinea Pig

Preservation of residual hearing during cochlear implantation is important. This study investigated changes in endocochlear potential (EP) during simulated cochlear implant (CI) electrode insertion. Laboratory animal study. Academic hospital laboratory. Guinea pigs were divided into 4 groups: cochleostomy only (4 animals), suction after cochleostomy (5 animals), simulated CI electrode insertion parallel to the longitudinal axis of the scala tympani without suctioning (7 animals), and simulated CI electrode insertion toward the modiolus without suctioning (7 animals). The EP was measured from the second turn of the cochlea, and the values after 20 minutes were compared. The EP showed little change at 20 minutes after cochleostomy with a nearly normal value of 84.83 ± 2.12 mV. Suctioning of the perilymph from the cochleostomy site caused a slight acute reduction in EP by about 6 mV, and the value at 20 minutes after cochleostomy was 78.64 ± 4.42 mV. Insertion of the simulated CI electrode parallel to the longitudinal axis of the scala tympani caused a slight decrease in EP to 78.91 ± 5.06 mV. Insertion toward the modiolus caused a marked decrease in EP to 54.13 ± 4.42 mV at 20 minutes after the treatment, significantly lower compared with the other 3 groups. EP was well preserved during carefully performed surgical procedures of simulated CI electrode insertion, but it decreased significantly if the simulated CI electrode was inserted toward the modiolus. Careful attention is necessary to ensure the correct direction of CI electrode insertion to preserve residual hearing. Use of suction should be minimized if possible.

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea, including an effect on the regulation of the endocochlear potential (EP). Noise-induced release of ATP into the endolymph activates a shunt conductance mediated by P2X(2) receptors in tissues lining the endolymphatic compartment, which reduces the EP and, consequentially, hearing sensitivity. This may be a mechanism of adaptation or protection from high sound levels. As inaction of such a process could contribute to hearing loss, this study examined whether the action of ATP on EP changes with age and noise exposure in the mouse. The EP and the endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged between 3 and 15 months. The EP and CoPR declined slightly with age with an associated small, but significant, reduction in auditory brainstem response thresholds. ATP (100-1,000 muM) microinjected into the endolymphatic compartment caused a dose-dependent decline in EP correlated to a similar decrease in CoPR. This was blocked by pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate, consistent with a P2X(2) receptor-mediated shunt conductance. There was no substantial difference in the ATP response with age. Noise exposure (octave-band noise 80-100 decibels sound pressure level (dBSPL), 48 h) in young animals induced an upregulation of the P2X(2) receptor expression in the organ of Corti and spiral limbus, most noticeably with the 90-dB exposure. This did not occur in the aged animals except following exposure at 90 dBSPL. The EP response to ATP was muted in the noise-exposed aged animals except following the 90-dB exposure. These findings provide some evidence that the adaptive response of the cochlea to noise may be reduced in older animals, and it is speculated that this could increase their susceptibility to noise-induced injury.

Endolymphatic sac is involved in the regulation of hydrostatic pressure of cochlear endolymph

To clarify the role of the endolymphatic sac (ES) in the regulation of endolymphatic pressure, the effects of isoproterenol, a beta-adrenergic receptor agonist, and acetazolamide, a potent carbonic anhydrase inhibitor, both of which decrease ES direct current potential on cochlear hydrostatic pressure, were examined in guinea pigs. When isoproterenol was applied intravenously, hydrostatic pressures of cochlear endolymph and perilymph were significantly increased with no change in endocochlear potential or the hydrostatic pressure of cerebrospinal fluid. Acetazolamide produced no marked change in the hydrostatic pressure of cochlear endolymph. In ears with an obstructed ES, the action of isoproterenol on the hydrostatic pressure of cochlear endolymph and perilymph was suppressed. These results suggest that the ES may regulate the hydrostatic pressure of the endolymphatic system via the action of the agents such as catecholamines on the ES.

Displacements of the organ of Corti by gel injections into the cochlear apex

In order to transduce sounds efficiently, the stereocilia of hair cells in the organ of Corti must be positioned optimally. Mechanical displacements, such as pressure differentials across the organ caused by endolymphatic hydrops, may impair sensitivity. Studying this phenomenon has been limited by the technical difficulty of inducing sustained displacements of stereocilia in vivo. We have found that small injections (0.5–2 μL) of Healon gel into the cochlear apex of guinea pigs produced sustained changes of endocochlear potential (EP), summating potential (SP) and transducer operating point (OP) in a manner consistent with a mechanically-induced position change of the organ of Corti in the basal turn. Induced changes immediately recovered when injection ceased. In addition, effects of low-frequency bias tones on EP, SP and OP were enhanced during the injection of gel and remained hypersensitive after injection ceased. This is thought to result from the viscous gel mechanically limiting pressure shunting through the helicotrema. Cochlear microphonics measured as frequency was varied showed enhancement below 100 Hz but most notably in the sub-auditory range. Sensitivity to low-frequency biasing was also enhanced in animals with surgically-induced endolymphatic hydrops, suggesting that obstruction of the perilymphatic space by hydrops could contribute to the pathophysiology of this condition.

Endolymphatic Perfusion with EGTA-Acetoxymethyl Ester Inhibits Asphyxia- and Furosemide-Induced Decrease in Endocochlear Potential in Guinea Pigs

We examined the effect of the Ca(2+) concentration in the endolymph ([Ca](e)) or in the endolymphatic surface cells ([Ca](i)) on the endocochlear potential (EP) by using an endolymphatic or perilymphatic perfusion technique, respectively. (i) A large increase in [Ca](e) up to approximately 10(-3) M with a fall in the EP was induced by transient asphyxia ( approximately 2 min) or by the intravenous administration of furosemide (60 mg/kg), and a significant correlation was obtained between the EP and p[Ca](e) (= -log [Ca](e), r = 0.998). (ii) Perfusion of the endolymph with 10 mM EGTA for 5 min neither produced any significant change in the EP nor altered the asphyxia-induced change in EP (DeltaEP(asp)), suggesting that neither [Ca](e) nor the Ca(2+) concentration gradient across the stria vascularis contributed directly to the generation of the EP in the condition of low [Ca](e). In contrast, endolymphatic perfusion with high Ca(2+) (more than 10 mM) produced a decrease in EP and a significant correlation was obtained between the EP and the Ca(2+) concentration of perfusion solution (r = 0.982), suggesting that Ca(2+) permeability may exist across the stria vascularis. (iii) The administration of a Ca(2+) chelator, EGTA-acetoxymethyl ester (AM, 0.3 mM), to the endolymph, which produced a gradual increase in EP, suppressed significantly, by 60-80%, DeltaEP(asp) or furosemide-induced changes in EP. In contrast, perilymphatic administration of 0.5 mM EGTA-AM caused no significant suppression of the DeltaEP(asp). These findings suggest that [Ca](i) plays an important role in generating/maintaining a large positive EP.

Acute endolymphatic hydrops generated by exposure of the ear to nontraumatic low-frequency tones.

Low-frequency sounds presented at high nontraumatizing levels induce temporary hyperacusis in humans and animals. One explanation of this finding is that the basilar membrane operating point may be disturbed by an endolymph volume change. This possibility was investigated using volume and flow markers iontophoresed into the endolymphatic space of guinea pigs. Marker concentrations were measured with ion-selective microelectrodes placed apically and basally to the iontophoresis site during exposure of the ear to low-frequency tones. Concentration changes were interpreted quantitatively using a finite-element model of the endolymphatic space that allowed changes of endolymph cross-sectional area and flow to be derived. Stimulation with a 200 Hz tone at 115 dB SPL for 3 min produced marker concentration changes consistent with the induction of transient endolymphatic hydrops and a basally directed displacement of endolymph. Endocochlear potentials were greater than normal after the exposure when hydrops was present. During identical tone exposures of animals without marker, we found that action potential (AP) threshold changes and endolymph potassium changes associated with the hydropic state were small. Marker concentration changes were compared with changes in endocochlear potential and AP thresholds for a range of exposure frequencies and levels. AP hypersensitivity occurred with 200 Hz exposure levels below those inducing endolymph volume disturbances. Endolymph volume changes are thought to be the result of, rather than the cause of, changes in operating point of the cochlear transducer. The observations that auditory threshold and endolymph potassium changes are minimal under conditions where substantial endolymphatic hydrops is present is relevant to our understanding of the hearing loss in patients with Meniere's disease.

Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea.

Noise exposure damages the stria and spiral ligament and may contribute to noise-induced threshold shift by altering the endocochlear potential (EP). The aim of this study was to correlate lateral wall histopathology with changes in EP and ABR thresholds. CBA/CaJ mice were exposed to octave band (8-16 kHz) noise for 2 h at intensities ranging from 94 to 116 dB SPL and evaluated 0 h to 8 weeks postexposure. EP in control mice averaged 86 and 101 mV in apical and basal turns, respectively. The 94 dB exposures caused a 40 dB temporary threshold shift (TTS), and there was with no corresponding change in EP. The 112 and 116 dB exposures caused >60 dB threshold shifts at 24 h, and EP was transiently decreased, e.g., to 21 and 27 mV in apical and basal turns after 116 dB. By 1 week postexposure, EP returned to control values in all exposure groups, although those exposed to 112 or 116 dB showed large permanent threshold shifts (PTS). Cochleas were plastic-embedded and serial-sectioned for light microscopic and ultrastructural analysis. Acute changes included degeneration of type II fibrocytes of the spiral ligament and strial edema. The strial swelling peaked at 24 h when significant EP recovery, had taken place, suggesting that these changes reflect compensatory volume changes. In the chronic state, massive loss of type II fibrocytes and degeneration of strial intermediate and marginal cells was observed with drastic reduction in membrane surface area. The results suggest that EP shifts do not occur with TTS and also do not add significantly to PTS in the steady state. However, EP loss could contribute to acute threshold shifts that resolve to a PTS. EP recovery despite significant strial degeneration may be partly due to decreased transduction current caused by hair cell damage.

Photochemically Induced Double Lateral Wall Lesions in the Guinea Pig Cochlea

ObjectiveMultiple patches of atrophy have been reported in the stria vascularis (SV) in elderly persons with presbycusis The aim of this study was to investigate the correlation between sensorineural hearing loss and this strial condition.Material and MethodsWe established a new animal model comprising two small lesions in the SV in the second turn of the cochlea by means of photochemical reaction. Using this model, we investigated morphological and physiological changes in the cochlea at 3, 7 and 14 days after SV damage.ResultsScanning electron microscopy studies revealed that the strial cells between the two damaged areas of the SV remained intact, although the outer hair cells (OHCs) facing the intact SV area were damaged. Furthermore, damage to the first and second rows of OHCs gradually progressed throughout the 14-day observation period. The endocochlear potential (EP) measured at a point midway between the 2 lesions at 3 and 7 days was found to be significantly lower compared with control values, but had returned to a normal level at 14 daysConclusionThe reversible EP change and localized OHC loss seen in the present investigation may help to understand acute idiopathic or progressive sensorineural hearing loss.

Changes in Off-lesion Endocochlear Potential Following Localized Lesion in the Lateral Wall

Endocochlear potential (EP) was measured at various off-lesion sites after a small focal lesion was made in the lateral wall of the guinea pig cochlea. Lesions were produced by a photochemical reaction between systemically administered rose bengal and focused green light illumination. In 21 ears, continuous measurement for 30 min after onset of the reaction at turns apical or basal to the site of illumination revealed no significant changes in EP compared with the control value (p<0.01). In another group of 43 ears, EP was measured at 3 days post-illumination. A significant decline was seen at every site located apical to the lesion (p<0.001). Conversely, no significant change was measured at any site located basal to the lesion. These findings suggest that the decrease in EP assumes the form of a gradient from the lower to upper turns in the guinea pig cochlea.

Longitudinal endolymph movements induced by perilymphatic injections

Endolymph movements and endocochlear potential (EP) changes were measured during disturbances of perilymphatic pressure, induced by injecting artificial perilymph into scala tympani (ST) or scala vestibuli (SV) of the guinea pig cochlea. Injections were performed either with or without an outlet made in the opposite perilymphatic scala. Injections into ST without an outlet induced large pressure changes but virtually no endolymph movement or EP change. Injection at the same rate into ST with an outlet in SV produced smaller pressure changes which were accompanied by a basally-directed displacement of endolymph and significant EP changes. The magnitude of endolymph displacements and EP changes varied as a function of injection rate. Injections into SV, either with or without an outlet in ST, produced apically-directed endolymph displacement and EP changes. For the SV injections without an outlet, the cochlear aqueduct and round window are likely to provide an outlet and compliance, permitting flow along the perilymphatic scalae to occur even when no ST outlet was provided. We conclude that endolymph movements are not dependent on the absolute pressure of the perilymph, but instead occur when small, sustained pressure gradients are present across the cochlear partition, corresponding to times when perilymph flow is induced. This study demonstrates that in the normal, sealed cochlea, endolymph and EP are insensitive to fluid injections into ST, but are sensitive to fluid injections into SV. Endolymph movements are therefore unlikely to be generated by cerebrospinal fluid pressure fluctuations (such as those produced by respiration, posture changes, coughing, sneezing, etc) which are transmitted to ST by the cochlear aqueduct.

An Electrophysiological Study of the Effects of Acute Methylmercury Chloride Exposure on the Function of the Guinea Pig Cochlea

The inner ear function of methylmercury chloride (MMC)-exposed guinea-pigs was examined in this study. Previous studies which investigated the function of the eighth cranial nerve and Corti-organ using cochlear microphonics (CM), compound action potential (CAP) and measurement of endocochlear potential (EP) reported ototoxicity following experimental exposure to MMC. In this report, the effect of MMC on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, action potential (AP), EP and K+ ion concentration of the endolymph. Guinea-pigs were injected with 5 mg/kg MMC (using 0.2% solution) twice a week for 1-3 weeks. The maximum output voltage of AP was decreased by injection of MMC (5 mg/kg × 6). A decrease in the CM maximum output voltage and the elevation of CM pseudothreshold was seen after MMC injection. Changes in EP during 3 min anoxia were observed, especially a decrease in the absolute value of the negative potential. The endolymph K+ ion concentration remained unchanged. These findings indicate that the diffusion potentials decreased and at the same time was reduced the maximum output voltage in CM induced by MMC injection (5 mg/kg × 6) in this experiment.

Effect of focal cochlear vascular lesion on endocochlear potential in guinea pigs

The alteration endocochlear potential (EP) in response to total cochlear ischemia induced by various experimental manipulations has been studied. However, the effect of restricted areal damage to the microvessels (restricted to small area in the lateral wall of a cochlear turn) on the EP value is still unknown. In the current investigation we adopted a photochemical method to produce a focal (i.e., restricted area) microvessel injury in the lateral wall of the guinea pig cochlea and examined the effect of these insults on EP recorded in the same region. The small area of the microvessel lesion (small fenestra: approximately 0.2 × 0.4 mm 2) induced by photoactivation did not yield significant EP changes, suggesting that damage to such a small area of microcirculation in the lateral wall of the cochlea has no statistically significant effects on EP values. In subjects with a large area of the microvessel lesion (large fenestra: ≈ 0.2 × 0.8 mm 2), a decrease in the EP value (mean ± SEM 7.9 ± 0.8 mV) was noted. However, the control group animals with a large fenestra but without microvessel lesion also displayed a decrease (8.6 ± 0.8 mV) in EP. In the current study we were unable to differentiate whether the EP changes in animals with the large fenestra microvessel lesions were caused by the cochlear blood flow decrease or by the surgical preparation. However, the results of this study indicated if the EP value was affected by the large area of the microvessel lesion, the level of decrease would not be large. That is, the EP decrease was less than the change in the control group (mean: 8.6 mV). Considering the dependence of EP on blood flow, the data of this study suggest that compensatory mechanisms in the cochlea may maintain the EP following a focal lesion in the lateral wall of the cochlea. This study also indicates that the photochemical method provides a reliable approach to produce the animal model with the focal microvessel lesion in the lateral wall of the cochlea.

Cochlear effects of indacrinone are not altered by penicillin

Indacrinone is a loop diuretic structurally related to ethacrynic acid. Indacrinone is a racemic mixture. Previous studies have shown that the (−) enantiomer caused reduction of endocochlear potential (EP) and elevation of compound action potential (CAP) threshold (Rybak and Whitworth, 1987a). It has been demonstrated that organic acids such as penicillin, probenecid and sodium salicylate prevent the reduction of EP normally observed after furosemide administration (Rybak et al., 1992a). The present study was designed to determine whether penicillin pretreatment could prevent changes in EP and CAP threshold in (−)-indacrinone treated chinchillas. Adult chinchillas were anesthetized with ketamine and pentobarbital. A microelectrode was advanced into the scala media using the round window approach, and CAP responses to clicks were measured. One group was treated with (−)-indacrinone 100 mg/kg via the jugular vein. A second group of animals received penicillin 50 mg/kg IV thirty minutes before (−)-indacrinone. The mean EP change in the indacrinone-treated animals was 38.38 ± 19.32 millivolts (mv). The reduction of EP in the group receiving penicillin was 24.43 ± 20.74 mv ( P > 0.09). The mean CAP threshold changes in animals receiving indacrinone was 20 ± 14.14 dB whereas those pretreated with penicillin showed a threshold shift of 21.43 ± 20.35 dB ( P > 0.05). These findings are consistent with previous studies which showed that the effect of ethacrynic acid on the EP and CAP was not changed by the pretreatment with penicillin (Rybak et al., 1990).

Vulnerability and adaptation of distortion product otoacoustic emissions to endocochlear potential variation.

The endocochlear potential (EP) was reversibly decreased in adult gerbils by the intraperitoneal injection of furosemide, while cochlear functioning was monitored by measurement of distortion production otoacoustic emissions (DPE) at a range of stimulus intensities. Stimulus frequencies for DPEs were f1 = 6.8 and f2 = 8 kHz (f2/f1 = 1.18). Emissions monitored in the ear canal and scala media were 2f1-f2, 3f1-2f2, 2f2-f1, and f2-f1. Typically, the EP decreased smoothly, reached a minimum one-half hour after injection, then recovered slowly over several hours. Emissions at 2f1-f2 and 3f1-2f2 at low stimulus levels were particularly vulnerable to the change in EP. These vulnerable emissions showed characteristic trajectories in which the amplitudes changed little with the initial EP decrease, then dropped sharply as the EP continued to decrease. However, the amplitudes then began to recover even before the EP reached minimum, and recovered completely while the EP remained subnormal. The trajectories of the other odd order emissions were similar, but lacked the abrupt decrease. The variation of the even order (f2-f1) component was completely different, but appeared related to the odd order trajectories in a complex fashion. During the initial decrease for the vulnerable components, the decrease in emission amplitude (in dB) was found to be proportional to the square of the change in EP (in mV). The recovery with a subnormal EP was interpreted as an adaptive effect with a time constant of about 15 min.

Effects of Adenylate Cyclase Activation on Electrical Resistance of Scala Media

Electrical resistance of scala media at the second turn of the guinea pig cochlea was measured while cochlear adenylate cyclase was activated by perilymphatic perfusion with 2 x 10(-4) M forskolin. The electrical resistance decreased from the pre-forskolin value (6.36 +/- 0.27 k omega to 5.22 +/- 0.33 k omega, n = 5), while the endocochlear potential (EP) increased from the pre-forskolin value (70.2 +/- 2.1 mV to 81.2 +/- 2.8 mV, n = 5). The time course of the electrical resistance change was more rapid than that of the EP change but almost identical to the time course of the change in the Cl- activity of the endolymph. The results suggest that the forskolin-induced decrease in the electrical resistance of the perilymph-endolymph barrier (presumably Reissner's membrane), and the consequent increase in Cl- flux into the endolymph may trigger EP elevation.

Organic acids do not alter the cochlear effects of ethacrynic acid

Previous studies have shown a reduction of the ototoxicity of furosemide in chinchillas pretreated with organic acid transport inhibitors. The current studies were designed to investigate whether such a protective effect could be observed in chinchillas receiving ethacrynic acid. Chinchillas weighing 400–600 g were injected with saline followed by ethacrynic acid 12.5 mg/kg i.v. (controls) or one of three organic acids (probenecid, penicillin G and or sodium salicylate) 50 mg/kg i.v., thirty minutes prior to ethacrynic acid injection (experimentais). Endocochlear potential (EP) and compound action potential of the eighth nerve (CAP) elicited by click stimuli were simultaneously monitored before and after injection in both groups. The mean change in EP and CAP findings are consistent with observations by other investigators of the actions of these loop diuretics in the isolated loop of Henle. In the latter tissues, the ‘ furosemide-like loop diuretics’ appear to have a different mechanism of action than does ethacrynic acid. It appears from the findings of the present study that the actions of furosemide and ethacrynic acid on the cochlea are by different mechanisms as well.

Changes in endocochlear potential during anoxia after intense noise exposure

Endocochlear potentials (EPs) were investigated in healthy guinea pigs and in those exposed to white noise of 125 dB SPL for 20–80 min. EPs were measured during and after temporary anoxia (3.5 min, denoted as reversible anoxia) and then during continuous anoxia to evaluate noise-induced changes in EP properties. Succino-dehydrogenase (SDH) activity and morphologic changes in hair cells were also evaluated in surface preparations of the hair cells. It was found that changes in EPs correlated with the duration of noise exposure. The longer the noise exposure, the greater the decrease in EPs. EPs could recover in one week post-exposure, in roughly the same time needed for recovery of SDH activity in hair cells. Noise exposure also resulted in some changes in EP dynamic behaviour during and after reversible anoxia, but did not cause any significant change in maximal negative EP. The mechanisms underlying these results are discussed.