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Model of d.c. potentials in the cochlea: effects of voltage-dependent cilia stiffness.

The purpose of this study was to explore possible mechanisms for the generation of the summating potential. Computer simulation was used to model the effects of potential hair cell nonlinearities on extracellular and intracellular d.c. potentials in the cochlea. No one nonlinearity can account for both extracellular and intracellular experimental data. However, a model which includes two nonlinearities (voltage-dependent cilia stiffness and nonlinear transducer channel resistance) produces extracellular and intracellular responses which match experimental data very well.

Animals↗

Electrically induced potentiation of eighth nerve responses.

Whole-nerve potentials were recorded from a total of 42 anesthetized cats using a 25-micron electrode in the 8th nerve as it exits from the internal auditory meatus, in response to acoustic clicks across an 80-db range. Biphasic electric pulses, 0.5 msec in duration, 100/sec for 5-10 min, at 100 microamps, were delivered by the 8th nerve electrode. Potentiation of responses to acoustic clicks was observed in amplitude, latency, and duration when comparing sets of pre- vs post-stimulation output. High consistency was achieved. These data were corroborated by recording output also from the round window, and by auditorily evoked brainstem far field potentials with a subcutaneous electrode. Control experiments such as ablation of AI, AII, EP, and IT, resection of the inferior colliculus, the crossed olivocochlear bundle, and middle-ear muscles, determined that electric potentiation was a local effect. Furthermore, the usual electric pulses applied to an electrode on the round window had no potentiating effect. Electric stimulation had a significant effect at the .001 level in increasing amplitude of response. Latency of N1 was shortened by 0.2 msec. Potentiation persisted for up to 3 hrs. An unexpected result was potentiation of 8th nerve and brainstem nuclei responses after acoustic stimulation of the contralateral ear; electric stimulation may induce a more active involvement of efferent activity originating in the superior olive or more rostrally. The interpretation of how such changes might affect perception after, for example, long term stimulation of neurons by a prosthesis is difficult to make without behavioral corroboration. The amplitude change of the whole-nerve action potentials are rough indicators of relative loudness. Thus an accentuated loudness may be experienced over time as equivalent intensities tend, as in these cats, to elicit greater response. The long time constancy of the decay, on the other hand, could tend to maintain a consistency of such potentiated responses and thus create no real variability in perception over time. The shortened latency could mean an involvement of higher frequency perception, but how this might be translated into a change in, for example, intelligibility of speech it is not possible to infer at this time.

Acoustic Stimulation↗

Cochlear electrically evoked emissions modulated by mechanical transduction channels.

Cochlear outer hair cells are capable of both mechanical-to-electrical and electrical-to-mechanical transduction. Vibration of their stereocilia by sound is believed to stimulate somatic motility via a receptor potential developed across the basolateral membrane, thereby enhancing the mechanical vibration and increasing the sensitivity and frequency selectivity of the ear. Extrinsic electrical currents, applied at the tops of the cells, also appear to activate motility in vivo, presumably after entering the cell. Earlier experiments suggested such currents might enter through the transduction channels themselves, but an alternative shunt pathway through the membrane capacitance seems more likely on physical grounds. We therefore recorded electrically evoked oto-acoustic emissions while modulating the transduction channels by driving them with low-frequency sound. Recordings of the low-frequency cochlear microphonic provided a measure of the mean electrical conductance through the channels during sound stimulation. Emissions increased during displacement of the basilar membrane toward scala vestibuli, when the channels were biased open, and decreased on the opposite phase, and the modulation of the emission was in direct proportion to the cochlear microphonic. The results are the strongest evidence yet that electrically evoked emissions are generated directly by mechanisms related to cochlear transduction and lead to the surprising conclusion that, for frequencies up to at least 12 kHz, extrinsic electrical currents enter the hair cell predominantly by the resistive pathway through the transduction channels. Alternatively, the results might be consistent with direct modulation of a motility source driven by capacitive currents but whose output depends on the state of the channels.

Animals↗

[Acoustic distortion products. Recordings from patients with normal hearing and those with sensorineural hearing loss].

Distortion product otoacoustic emissions (DPEs) are a subtype of evoked otoacoustic emissions that represent a class of cochlear response. Because of their frequency specificity and the wide range of frequencies explored DPEs have a great potential for clinical use. DPEs studies include DP-audiograms and input/output functions. We recorded 27 DPEs, 24 of them from normal ears and 3 from pathological ears. This report resumes methods and results.

Acoustic Stimulation↗

Effects of a calcium channel blocker and calcium chelating agents on cochlear electrical activity in the guinea pig.

Endocochlear potential (EP) in the guinea pig was investigated under the influence of nifedipine and calcium chelating agents. The area from the scala tympani to the scala vestibuli was perfused with control and test solutions. EP decreased gradually after perfusion with the nifedipine solution, when the concentration was higher than 100 ng/ml. At a concentration of 200 ng/ml, EP decreased from +70 mV to +14 mV. At 1000 ng/ml, it decreased from +70 mV to +54 mV and stayed at this level during perfusion. It began to return to the initial level when perfusion with the control solution was recommenced. Cochlear microphonics (CM) also decreased with 200 ng/ml of nifedipine, but less markedly than EP. EGTA (10 mM) decreased EP from +80 mV to +67 mV. This change, however, was only transient and EP returned to the control level. EDTA (4 mM) had no significant effect on EP. These results suggest that Ca ions play a role in maintaining EP in a manner similar to that by which Ca modulates Na-K pump activity of the marginal cells in stria vascularis.

Animals↗

Interaction of aminooxyacetic acid and ethacrynic acid with intense sound at the level of the cochlea.

Results of previous investigation of the interaction of intense sound and drugs have, in general, failed to show a protective effect mediated by pre-administration with a drug having transient ototoxic effects. The present investigation was designed to further evaluate a protective effect found previously at the anatomical level and explained with an electrochemical theory of noise damage. The alternating current (a.c) potential and compound eighth nerve action potential (CAP) amplitude were monitored in aminooxyacetic acid (AOAA)- or ethacrynic acid (EA)-treated guinea pigs exposed to either moderate or high levels of intense sound and compared to changes observed in the same potentials in animals exposed to the intense sounds alone. Results showed protective effects only in the moderate--intense sound-exposure groups, with changes in sensitivity and voltage on the linear part of the input--output curve of the a.c cochlear potential found to be the only conditions where differences occurred. These results were difficult to interpret in terms of a protective effect and point to the need for obtaining additional data before an electrochemical mechanism is shown to play a role in the effect of intense sound on the cochlea.

Acetates↗

Evoked potential correlates of echolocation in the mustached bat, Pteronotus p. parnellii.

The biosonar signals of the greater mustached bats are characterized by a long constant frequency component that is preceded and terminated by frequency modulated components. It has generally been concluded that the terminal FM (TFM) is important for target ranging while the initial FM (IFM), or beginning of the signal, is relatively insignificant. With the aid of chronically implanted electrodes, acoustically evoked brainstem potentials were recorded from bats during simulated flight on a pendulum and when targets were placed at fixed distances from the bat's head. Distinct pulse- and echo-evoked potentials were recorded in relation to the onset of both the IFM and TFM, or the onset of the CF when no IFM was present. Echo-evoked potentials were often as high in amplitude as pulse-evoked potentials and the timing of the IFM- and TFM-pulse and echo-evoked potentials seemed to accurately reflect target distance. Data indicate that the IFM, or signal onset, must be a significant part of the echo even though it is usually faint, overlaps the intense outgoing CF component, and returns to the ear when the middle ear muscles are contracting.

Animals↗

Calcium transport mechanism in the endolymph of the chinchilla.

The Ca2+ transport mechanism between endolymph and perilymph was evaluated by the effects of vanadate and amiloride on the endocochlear potential (EP) and the Ca2+ concentration in endolymph using Ca2+-selective microelectrodes. Under normal conditions, the EP was 81.8 +/- 0.9 mV, and the Ca2+ concentrations in endolymph and perilymph were 16.6 +/- 1.3 microM and 1.85 +/- 0.11 mM (N = 12), respectively. Therefore, the uphill electrochemical potential gradient for Ca2+ from perilymph to endolymph, 20.2 +/- 2.0 mV, indicates the existence of an active uptake of Ca2+ into endolymph. Vanadate, the inhibitor of Ca2+-ATPase, topically applied to the round window membrane caused biphasic changes of the EP and the endolymph Ca2+ concentration; the former in a transient increase followed by a consistent decrease and the latter in a slow decrease followed by a slow increase. Amiloride induced a slight EP depression and a concomitantly slight elevation of the Ca2+ concentration in endolymph. The electrochemical potential gradient for Ca2+ between endolymph and perilymph vanished with the use of vanadate but was not affected by amiloride. These results suggest that Ca2+-ATPase, sensitive to vanadate, maintained the bulk of active Ca2+ transport in the cochlea and that the participation of Na+-Ca2+ exchange is negligible.

Amiloride↗

NompC TRP channel required for vertebrate sensory hair cell mechanotransduction.

The senses of hearing and balance in vertebrates rely on the sensory hair cells (HCs) of the inner ear. The central element of the HC's transduction apparatus is a mechanically gated ion channel of unknown identity. Here we report that the zebrafish ortholog of Drosophila no mechanoreceptor potential C (nompC), which encodes a transient receptor potential (TRP) channel, is critical for HC mechanotransduction. In zebrafish larvae, nompC is selectively expressed in sensory HCs. Morpholino-mediated removal of nompC function eliminated transduction-dependent endocytosis and electrical responses in HCs, resulting in larval deafness and imbalance. These observations indicate that nompC encodes a vertebrate HC mechanotransduction channel.

Amino Acid Sequence↗

Characterization of an EPSP-like potential recorded remotely from the round window.

The whole-nerve cochlear action potential (CAP), to tone burst stimulation, was recorded before and after application of tetrodotoxin (TTX) to the intact round window (RW) membrane. TTX abolished the CAP leaving a residual negative potential without altering the summating potential (SP) or the cochlear microphonic (CM). The residual potential retained its polarity when recorded from scala vestibuli. The peak latency, amplitude, and tuning properties of the residual potential showed features similar to the CAP. Application of kainic acid to the RW membrane eliminated the residual potential, leaving the SP and CM unaltered. It is hypothesized that the sources of the residual potential are the excitatory post-synaptic potentials from the peripheral processes of afferent dendrites under the inner hair cells.

Acoustic Stimulation↗

The time course of the strial changes produced by intravenous furosemide.

The ultrastructural abnormalities produced in the stria vascularis by intravenous furosemide (80 mg/kg) were investigated in 14 guinea pigs. The changes consisted of marginal cell swelling, shrinkage of the intermediate cells and enlargement of the intercellular spaces, as described in other intoxications. The cytological derangements (including characteristic dilatation of the Golgi membranes) differed in detail from those arising after a comparable dose of ethacrynic acid. The morphological alterations were already present at 2 min, were maximal at 10 min, recovered only slowly at first and had not disappeared entirely at 180 min. For comparison, the fall in the endocochlear potential had a latent period of 20 s and was greatest at 2.3 min; its recovery was rapid initially but also incomplete at 180 min. Thus, no gross discrepancy in the time courses occurred, even if the correlation was imperfect. That reported previously must be due, therefore, to the much longer delays found following intraperitoneal administration.

Animals↗

Characterization of potassium permeability of cochlear duct by perilymphatic perfusion of barium.

The relative transepithelial "permeabilities" of the cochlear duct to K, Na, and Cl were investigated so as to identify the K-selective tissues and to determine the cellular origin of this selectivity. Single-ion substitutions were made for K, Na, and Cl with the impermeant species N-methyl-D-glucamine (NMDG) for K and Na and gluconate or sulfate for Cl in perilymph. Transepithelial potential changes were relatively slow and small for Na and Cl substitutions. However, either K for Na or K for NMDG substitutions demonstrated a pronounced K selectivity (rapid changes of electrical potential) of only the sensory-cell tissue (organ of Corti). The response to the K for Na substitution was most clearly seen after electrogenic K transport was inhibited by ischemia while the sensory cells were metabolically sustained via perilymphatic perfusion. Under this condition, perfusion of a medium containing 154 mM K gluconate reduced the negative potential (typically -25 to -40 mV) to within a few millivolts of zero. In a control medium, perilymphatic barium (0.5-5 mM) produced qualitatively similar effects, suggesting that this K selectivity is localized primarily at the basolateral membrane of the sensory cells rather than at the junctional complexes.

Animals↗

[Effect of potassium channel opener, Nicorandil, on cochlear electrical potentials in the guinea pig].

It is commonly accepted that the endocochlear DC potential (EP) of the cochlea is generated by electrogenic transport of potassium ion into the scala media from the marginal cells of the stria vascularis. In recent years, many models of the marginal cell have been developed in which the EP is generated by an electrogenic ion transport system localized in either the basal or apical membranes of the marginal cell. On the other hand, Salt et al. reported that EP cannot be generated by the marginal cells alone but, rather, may involve passive potassium movement across the apical membranes of basal cells. In this study, the effect of Nicorandil, a potassium channel opener, on EP and cochlear microphonics (CM) were investigated by perfusion through the perilymphatic space of the guinea pig from the scala tympani to the scala vestibuli with an artificial perilymph. The results of several concentrations were examined. Characteristic of Nicorandil, a vasodilatory agent, is an increase in membrane potassium conductance due to the opening of plasmalemma ATP-regulated K+ channels in cardiac muscle and vascular smooth muscle. This effect results from the membrane hyperpolarization and consequent reduced opening probability of voltage-dependent Ca2+ channels. When the perilymphatic space was perfused with a solution containing 1 x 10(-4) M Nicorandil, the EP level decreased from 74.8 +/- 2.4mV to +50.0 +/- 12.8mV and the CM amplitude fell to 78.6% of the control. At a concentration of 5 x 10(-4) M, EP decreased from 77.8 +/- 4.1mV to 47.0 +/- 7.6mV and CM amplitude fell to 16.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Retrolabyrinthine vestibular neurectomy with simultaneous monitoring of eighth nerve and brain stem auditory evoked potentials.

We have used retrolabyrinthine vestibular neurectomy in 36 of 49 cases as the primary surgical procedure to relieve vertigo. Most of the patients (46 of 49) had Meniere's disease. Results indicate that 71% (35 of 49) of the patients had no vertigo after the operation, while 22% (11 of 49) had much improvement. Hearing was maintained within 20 dB of the preoperative level in 78% (38 of 49) of the patients. During surgery in the last 23 patients, direct nerve potentials were recorded from the middle ear promontory and the intracranial cochlear nerve. Brain stem auditory evoked responses were simultaneously recorded in the last 10 patients. It appears that the intraoperative direct cochlear nerve potentials can be used as a sensitive monitor of trauma to the cochlear nerve during and after vestibular neurectomy. If the latency of the eighth nerve action potential changes less than 0.3 msec and the waveform does not change after vestibular neurectomy, there is an excellent chance that hearing at 1 month after surgery will be within 15 dB of the level before surgery. The retrolabyrinthine vestibular neurectomy has replaced the middle fossa vestibular neurectomy and the endolymphatic subarachnoid shunt procedure in our clinic.

Brain Stem↗

Auditory physiology and behavior in RB/1bg, RB/3bg, and their F1 hybrid mice (Mus musculus): influence of genetics, age, and acoustic variables on audiogenic seizure thresholds and cochlear functions.

In the early 1950s, Frings and Frings began a process of selection for audiogenic seizure susceptibility and resistance in albino mice. The present study was conducted to examine behavioral and cochlear functions in the inbred descendants of these mice. The cochlear action potential (AP) thresholds of the susceptible RB/1bg inbred mice were abnormally high, and the resistant inbred RB/3bg mice had normal AP audiograms. The F1 hybrid showed heterosis for its cochlear function. Only the RB/1bg was susceptible to audiogenic seizures on the first acoustic exposure. Thresholds for the successive components of their audiogenic seizures were determined in response to narrow bands of noise. These paralleled the AP thresholds of RB/1bg mice (r = .89). This RB/1bg mouse showed little age-related cochlear loss, which probably accounts for its robust sensitivity to audiogenic seizures over most of its lifespan. Earlier studies had demonstrated that the susceptible RB line had a robust AP, but little or no cochlear microphonic (CM). The susceptible RB/1bg had well-defined AP and CM responses at low frequencies. The nonsusceptible RB/3bg mice were more resistant to acoustic priming than another mouse (CBA/J) strain with a similar audiometric profile.

Acoustic Stimulation↗

Cerebellar interaction with the acoustic reflex.

The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

Animals↗

Prolonged maintenance of endocochlear potential by vascular perfusion with media devoid of oxygen carriers.

A method is described for maintaining the cochlear potentials of the guinea pig via arterial perfusion of the surviving inner ear with an artificial medium devoid of oxygen carriers or oncotic agents. The endocochlear potential (EP) can be maintained at a normal level for periods in excess of 5 h; the responses of the EP to anoxia and to furosemide closely approximate those seen in the intact animal. This preparation may represent a simplified method for carrying out selected arterial perfusion experiments in the surviving inner ear.

Animals↗

Ototoxicity of indacrinone is stereospecific.

Indacrinone (MK-196) is a loop diuretic which consists of a racemic mixture. The purpose of this study was to evaluate the individual enantiomers in the chinchilla model to determine whether these compounds affect auditory function and whether a difference in ototoxic potency exists. Very little change of endocochlear potential (EP) or compound action potential (CAP) was noted in animals receiving the (+)-enantiomer. On the other hand, chinchillas injected with the (-)-enantiomer were found to have a dose related reduction in both CAP and EP. These findings suggest the possibility that the diuretic receptor in the kidney and the receptor mediating ototoxicity in the cochlea, may have similar steric requirements for interacting with loop diuretics.

Animals↗