Cochlear Action Potential Research Articles

Persistent hair cell malfunction contributes to hidden hearing loss

Noise exposures that result in fully reversible changes in cochlear neural threshold can cause a reduced neural output at supra-threshold sound intensity. This so-called “hidden hearing loss” has been shown to be associated with selective degeneration of high threshold afferent nerve fiber-inner hair cell (IHC) synapses. However, the electrophysiological function of the IHCs themselves in hidden hearing loss has not been directly investigated. We have made round window (RW) measurements of cochlear action potentials (CAP) and summating potentials (SP) after two levels of a 10 kHz acoustic trauma. The more intense acoustic trauma lead to notch-like permanent threshold changes and both CAP and SP showed reductions in supra-threshold amplitudes at frequencies with altered thresholds as well as from fully recovered regions. However, the interpretation of the results in normal threshold regions was complicated by the likelihood of reduced contributions from adjacent regions with elevated thresholds. The milder trauma showed full recovery of all neural thresholds, but there was a persistent depression of the amplitudes of both CAP and SP in response to supra-threshold sounds. The effect on SP amplitude in particular shows that occult damage to hair cell transduction mechanisms can contribute to hidden hearing loss. Such damage could potentially affect the supra-threshold output properties of surviving primary afferent neurons.

O3-E-20. Intraoperative cochlear nerve mapping by cochlear nerve action potential

Methods for intraoperative mapping of the cochlear nerve (CN) in surgery for acoustic neurinoma (AN) have not yet been established. We attempted intraoperative mapping of the cochlear nerve by cochlear nerve action potential (CNAP) with a new recording probe. The subjects were 10 patients who had undergone surgery for AN using a retrosigmoid approach. Three of the 10 patients had severe hearing impairment so that CNAP data could not be obtained. In six of seven patients with useful hearing acuity, CN could be identified during surgery. However, CNAP was obtained in the nerves adjacent to CN. We could identify CN by the difference in waveforms between CN and the adjacent nerves. The recording probe was appropriate for mapping, but was inappropriate for functional monitoring. In contrast, conventional electrodes were more suitable for functional monitoring, but were not suitable for mapping. The combination of these electrode types would greatly improve the accuracy of monitoring. We performed CNAP by monopolar and bipolar recording. In bipolar recordings, the signal to noise ratio was higher than that in the monopolar recordings. The combination of monopolar and bipolar recordings would also improve the accuracy of monitoring.

Electrocochleography in Round Window Vibrant Soundbridge Implantation

To determine the role of intraoperative electrocochleography to optimize the fitting of the floating mass transducer of the Vibrant Soundbridge on the round window membrane in patients with conductive and mixed hearing loss. Prospective cohort study. Tertiary referral center, Otolaryngology Department, University of Verona, Verona, Italy. Twenty-six adult patients suffering from chronic otitis media with moderate to severe conductive and mixed hearing loss, all with previous unsuccessful functional surgery, underwent round window vibroplasty. Thirteen subjects had intraoperative compound cochlear action potentials measured to assess vibroplasty coupling during and after surgery. In these patients, surgery was modified according to electrocochleographic feedback. The other 13 had vibroplasty without electrocochleography monitoring. The average preoperative air conduction and bone conduction thresholds (0.5-4 kHz) were not statistically significantly different between the 2 cohorts (P > .05). Compound action potential recordings indicated specific surgical modalities to optimize coupling of the floating mass transducer with the round window membrane. The average postoperative Vibrant Soundbridge-aided air conduction threshold improvements (0.5-4 kHz) were 54.6 ± 8.9 and 41.7 ± 11.1 dB HL, respectively, in the monitored and unmonitored cohorts (P = .0032). Improved round window vibroplasty outcomes are observed when the surgeon is promptly informed of the compound action potential changes induced by the floating mass transducer round window membrane vibroplasty and alters surgery accordingly. The key point for optimal coupling is a floating mass transducer in full contact with the round window membrane, free to vibrate without any contact with the surrounding bony structures and mobile footplate.

W3.4 Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones

W3.4 Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones

Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation

Intratympanic (IT) delivery of drugs to the ear is increasingly used for both clinical and research purposes. One limitation of IT delivery is that drugs are rapidly lost from the middle ear by a number of processes, so that prolonged delivery of drug is technically difficult. In the present study, the delivery characteristics of a poloxamer hydrogel formulation containing dexamethasone (dex) were evaluated. The gel is liquid at room temperature, allowing IT injection, but transitions to a gel at body temperature, providing a prolonged residence time in the middle ear. A 50-µl volume of control or dex-containing gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear function was assessed with cochlear action potential and acoustic emission thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24-hour treatment with dex-gel, perilymph drug gradients along the cochlea were assessed by taking samples sequentially from the apex, and endolymph was sampled from the basal turn. Control gel injections caused small changes in sound field calibrations and functional measures for low-frequency stimuli, consistent with an induced conductive loss. Within 24 h, responses returned to normal. Twenty-four hours after dex-gel injection, low-frequency changes remained as the dex-gel was retained better in the middle ear, but there was no indication of high-frequency loss. While perilymph sample data showed that dex gradients were substantially lower than after single injections of dex solution, quantitative analysis of this result suggests that some dex may have entered the perilymph through the thin bone in the apical region of the cochlea. Endolymph levels of dex remained lower than those in the perilymph. This study confirms that a poloxamer hydrogel-based dex formulation provides an effective method for a prolonged delivery, providing a more uniform distribution of drug in the inner ear.

Long term effects of BAPTA in scala media on cochlear function

BAPTA was iontophoresed or allowed to diffuse into the scala media of the first turn of the guinea pig cochlea via pipettes inserted through the round window and basilar membrane. Cochlear action potential (CAP) thresholds for basal turn frequencies were elevated, scala media cochlear microphonic in response to a 207 Hz tone were drastically reduced and the distortion products 2 f1– f2 and f2– f2 in response to primaries set at 18 and 21.6 kHz were eliminated or severely reduced. The animals were recovered and the above measurements repeated between 24 and 240 h after the application of BAPTA. In all animals thresholds for basal turn frequencies remained elevated, and the distortion components were severely reduced. The endolymphatic potential (EP), measured through the basilar membrane on recovery, was not significantly different from the values measured before BAPTA was applied. If the effect of BAPTA, in lowering endolymphatic Ca 2+ concentration, is restricted to the destruction of tip links, as has been shown in many other preparations, then these results suggest that this effect has permanent consequences, either because the tip links failed to regenerate or because their destruction precipitated the degeneration of OHCs. These results may have a bearing on the mechanisms behind permanent threshold shift.

Gender as a Predictor of Hearing Preservation Outcome in Acoustic Neuroma Surgery

Introduction: The correlation between gender and likelihood of preservation of serviceable postoperative hearing in acoustic neuroma surgery has seldom been reported. The limited available data suggest that, when preoperative tumor size and hearing are comparable, males have a greater likelihood of preservation of some postoperative hearing (p < 0.05 at best). Methods: A consecutive series of 184 retrosigmoid procedures for removal of unilateral acoustic neuromas (AN), in the period ending June 30, 2005, were subjected retrospectively to linear regression analysis for factors predictive of successful postoperative preservation of Gardner and Robertson Class 1 and 2 hearing (HP). These cases were selected on the basis of size (mean extracanalicular diameter < 20 mm) and preoperative hearing, and form part of a larger series of 810 consecutive cases of unilateral AN. Variables examined included age, gender, side and size of tumor, preoperative hearing, and intraoperative cochlear nerve compound action potential (CAP) threshold shift. Results: Overall HP rate was 34.4% (53.8% for intracanalicular AN). Size (p < 0.001), intraoperative CAP threshold shift (p < 0.0001), and female gender (p = 0.01) were predictors of HP. Male-female ratio for the series was 47/53. Age (p = 0.37) and tumor size (p = 0.20) did not differ between males and females. Postoperative HP occurred in 25.4% of males and 44.2 % of females, respectively (p = 0.01). Conclusions: Though female gender has not previously been identified as a predictor of greater likelihood of preservation of serviceable postoperative hearing in AN surgery, the present study strongly suggests that this is the case. Gender difference should probably be taken into account in preoperative discussion of outcome, at least in our hands, and may have other implications as well.

Does BAPTA leave outer hair cell transduction channels closed?

The calcium chelator BAPTA was iontophoresed into the scala media of the second turn of the guinea pig cochlea. This produced a reduction in low frequency cochlear microphonic (CM) measured in scala media and an elevation of the cochlear action potential (CAP) threshold that lasted for the duration of the experiment. Using two pipettes, one filled with KCl and the other KCl and BAPTA (50, 20 and 5 mM) it was possible to observe the effect of passing current through one electrode while measuring the endolymphatic potential (EP) with the other. The results demonstrated that current passed via the BAPTA pipette caused a sustained increase in EP of 8.2, 12.9 and 7.8 mV in the three animals used. This increase coincided with the decrease in low frequency CM that indicated a causal connection between the two. In a second series of experiments, pipettes with larger tips were inserted into scala media in the first cochlear turn and BAPTA was allowed to diffuse from the pipette. The results confirmed the relationship between EP increase and the fall of scala media CM. One interpretation of these results is that lowering the Ca 2+ concentration of endolymph with BAPTA inhibits mechano-electrical transduction in outer hair cells (OHCs) and leaves the hair cell transduction channels in a closed state, thus increasing the resistance across OHCs and increasing the EP. These findings are consistent with a model of hair cell transduction in which tension on stereo cilia opens the transduction channels.

Electrophysiological measurement method and system for positioning an implantable, hearing instrument transducer

An electrophysiological measurement method and system is provided for positioning an implantable transducer of a hearing instrument relative to a middle ear component or inner ear of a patient. The method and system employ electrophysiological measurement signals obtained in response to test signals applied to an implanted transducer. In one embodiment, the electrophysiological measurements are obtained by an electrocochleography measurement device that measures the cochlear summating potential and/or action potential responsive to test signals applied to an implanted transducer. In another embodiment, an auditory brainstem response measurement device is utilized to obtain electrical potential measurement signals responsive to test signals applied to an implanted transducer.

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain

We have injected by iontophoresis 4-amino-pyridine, a K + channel blocker and BAPTA, (a Ca ++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.

Otic microprobe for neuro-cochlear monitoring

A microprobe useful for assessing auditory function by enabling clinical and intraoperative measurements of blood flow, particularly cochlear blood flow and neural compound action potentials, particularly of the auditory nerve (cranial nerve VIII) is disclosed. In addition, a monitoring system containing this microprobe and a method of using the microprobe are described.

Ototoxic side-effects of the I Ks-channel blocker HMR1556

The inhibitor of I Ks-channels, HMR1556, a potentially antiarrhythmic drug, might possess ototoxic side-effects. The I Ks-channels are not only expressed in the heart but also in the stria vascularis of the inner ear and in the dark cells of the vestibular organ. Therefore possible effects of HMR1556 on hearing were studied in cats. Thresholds and intensity function of the cochlear action potential (CAP) were used as criteria. In addition to effects of the drug on heart rate and ECG, a substantial elevation of hearing thresholds and a shift in CAP intensity functions were observed. There was a clear dose–effect relationship. The hearing impairment observed showed a tendency for recovery. It is concluded that inhibitors of I Ks-channels may generally exert ototoxic effects provided they can reach the cochlear spaces.

Cysteine-string protein in inner hair cells of the organ of Corti: synaptic expression and upregulation at the onset of hearing.

Cysteine-string protein is a vesicle-associated protein that plays a vital function in neurotransmitter release. We have studied its expression and regulation during cochlear maturation. Both the mRNA and the protein were found in primary auditory neurons and the sensory inner hair cells. More importantly, cysteine-string protein was localized on synaptic vesicles associated with the synaptic ribbon in inner hair cells and with presynaptic differentiations in lateral and medial olivocochlear terminals -- the cell bodies of which lie in the auditory brainstem. No cysteine-string protein was expressed by the sensory outer hair cells suggesting that the distinct functions of the two cochlear hair cell types imply different mechanisms of neurotransmitter release. In developmental studies in the rat, we observed that cysteine-string protein was present beneath the inner hair cells at birth and beneath outer hair cells by postnatal day 2 only. We found no expression in the inner hair cells before about postnatal day 12, which corresponds to the period during which the first cochlear action potentials could be recorded. In conclusion, the close association of cysteine-string protein with synaptic vesicles tethered to synaptic ribbons in inner hair cells and its synchronized expression with the appearance and maturation of the cochlear potentials strongly suggest that this protein plays a fundamental role in sound-evoked glutamate release by inner hair cells. This also suggests that this role may be common to ribbon synapses and conventional central nervous system synapses.

Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy.

To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.

Properties of derived cochlear action potentials in forward tonal masking in guinea pigs.

Chronic experiments on guinea pigs were used to study the characteristics of cochlear nerve action potentials and the derived potential in conditions of forward masking. The auditory nerve action potential was recorded from the round window of the cochlea. The derived potential was obtained by subtracting the action potential recorded with masking from the response obtained in silence. These studies showed that the derived potential showed higher sensitivity to masking than the traditional measure of masking, i.e., the decrement in the amplitude of the auditory nerve action potential. The derived potential reflects not only changes in the action potential during masking, but also changes in its shape. Differences between the derived potential and the action potential decrement provide evidence that the amplitude and time changes in the derived potential provide more complete information on the nature of activity in the auditory fibers.

Is the round window membrane a portal for bacterial toxins? A putative mechanism for sensorineural hearing loss following acute otitis media

Aim: To investigate the hypothesis that bacterial toxins produced in the middle ear during acute otitis media (AOM), travel via the round window membrane (RWM) to cause cochlear damage and hence sensorineural hearing loss (SNHL). Methods: We investigated toxins produced by the two most common pathogens isolated from middle ear effusions in children. These were Pneumolysin, a product of S. pneumoniae and a cytoplasmic extract of Haemophilus influenza. Both electrophysiological measurements and morphological investigations were made after these toxins were placed on the RWM of guinea pigs. Control experiments were done using artificial perilymph as a substitute for the toxins. In each experiment one of the cochleas served as an internal control. Results: Losses in both the Cochlear Microphonics (CM) and Compound Action Potential (CAP) were observed indicating impaired hair cell function resulting in SNHL. Morphological studies showed hair cell destruction. Examination of the RWM exposed to pneumolysin showed disruption of this three-layered structure. Conclusions: The RWM is a probable portal for access to the inner ear by substances produced during AOM. Sensorineural hearing loss could result from the type of damage observed. More experiments are needed to verify this hypothesis and to determine the extent of damage that can be caused by these substances, especially with regard to the position of the damaged hair cells. Most of the damage observed occurred in the basal turn. Careful audiological examination (especially at high frequencies) of children who suffer with AOM might reveal a population of children with sensorineural hearing loss which might otherwise go undetected.

Experimental Study on the Effects of Gentamicin Injection on the Guinea-pig: Electrophysiological Studies

The inner ear distortion induced by gentamicin (GM), a type of aminoglycoside antibiotic, was examined in guinea-pigs. Previous studies which investigated the function of the eighth cranial nerve and organ of Corti using cochlear microphonics (CM) and compound action potential (CAP) reported ototoxicity following experimental exposure to GM. In this report, the effects of GM on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, CAP, summating potentials induced by 90 dB (SPL) tone burst, endocochlear potential (EP) and K+

Quantitative differences in endolymphatic calcium and endocochlear potential between pigmented and albino guinea pigs

A number of previous studies have suggested that melanin may play a role in Ca2+ homeostasis of endolymph. In the present study, endolymph Ca2+ levels and endocochlear potential (EP) were measured in all four cochlear turns of pigmented or albino guinea pigs. Auditory sensitivity was also evaluated using cochlear action potential (AP) thresholds. In pigmented animals we found that endolymph Ca2+ tended to increase from base to apex of the cochlea, while EP systematically decreased towards the apex. In contrast, no significant Ca2+ gradient was found in albinos and the EP decline was far less. As a result, the apical turn of albino animals had significantly lower Ca2+ and significantly higher EP than in pigmented animals. AP thresholds pooled across all test frequencies were significantly lower in albino animals although no differences at individual frequencies reached significance. Even after correction for EP differences, the endolymph Ca2+ levels in albino animals were significantly lower than in pigmented ones. These results confirm that there are significant physiologic differences between pigmented and albino animals, which are a likely consequence of the absence of melanin in the albino cochlea. They are consistent with the involvement of melanin in the active transport of Ca2+ into endolymph.

Expression and function of adenosine receptors in the chinchilla cochlea

Previous studies indicate the presence of adenosine receptors in the cochlear tissues obtained from different animals. This study was initiated to determine the subtypes of adenosine receptor (AR) present in the chinchilla cochlea and to assess their function. Radioligand binding studies demonstrate the presence of both the A1 AR and A3AR in membranes prepared from the cochlea, using the radioligands [3H]DPCPX and [125I]APNEA. Estimates of the number (Bmax) of A1AR and A1AR plus A3AR by saturation curves were 118 ± 13 and 417 ± 120 fmol/mg, respectively, with the respective equilibrium dissociation constants (Kd) averaging 2.7 ± 0.2 and 26.3 ± 13.8 nM. No significant number of A2aAR were detected using [3H]CGS21680. The nonhydrolyzable adenosine analog R-phenylisopropyladenosine (R-PIA, 1 μM) elicited a small but significant degree of inhibition of forskolin-stimulated adenylyl cyclase activity (10.4 ± 2.5%) in cochlear membrane preparations, which was insensitive to blockade by theophylline (100 μM). Furthermore, R-PIA elicited an increase in inositol 1,4,5-trisphosphate production in dissociated cell preparations obtained from the cochlea. No significant effect of R-PIA was observed on auditory measures such as auditory brainstem evoked response, cochlear action potential and endocochlear potential following round window application. However, round window application of R-PIA elicited significant increases in the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and significantly reduced the levels of malondialdehyde, a marker of lipid peroxidation. These results suggest a potential cytoprotective role of adenosine in the cochlea against oxidative damage.

The Mechanism and Site of Action of Lidocaine Hydrochloride in Guinea Pig

Lidocaine was applied to the round window (RW) in order to localize its site of action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and compound action potential (CAP) input/output functions were measured to a 16 kHz tone burst to assess the functional changes of the cochlea. In separate experiments, the effect of lidocaine on the whole cell current of isolated outer hair cells (OHC) was studied. A dose of 2 μl of 40 mM lidocaine in saline solution, when applied to the RW, caused a small change in all measured variables, indicating a passage of the drug through the RW membrane to sites of action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total of 40% from the control. A partial recovery occurred for CM during the 30 min follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine decreased the whole cell current in a dose-dependent fashion. The KD for lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an additional specific effect of lidocaine on the cochlear nerve and/or on inner hair cells. Considering that lidocaine alters OHC current (in isolated hair cells) and that lidocaine does not affect endocochlear potential [Laurikainen et al. Acta Otolaryngol (Stockh) 1991; 112: 800-9], the observed CM changes are most likely due to an in vivo effect on OHCs Thus, the early effect of lidocaine on the cochlea appears to be due to a significant change in organ of Corti function, rather than to direct anesthesia of the cochlear nerve. Later, an independent effect of the drug may occur on neural tissues in the inner ear.