The French National Cochlear Implant Registry (EPIIC): Cochlear implantation in adults over 65years old.

OBJECTIVES: To analyze the performance of cochlear implants in French patients aged 65 and over, implanted between 2012 and 2016, using data from the French national registry for cochlear implants (EPIIC). MATERIALS AND METHODS: The French national registry incorporates patient data from before implantation and for three years after implantation, stratified in different age groups (18-39, 40-64years, 65-74years and>75years). Here, we assessed the latter two categories. Hearing was assessed using mono- and disyllabic words in a silent background. The Category of Auditory Performance (CAP) scale was also implemented and subjects took the Abbreviated Profile of Hearing Aid Benefit (Aphab) questionnaire. RESULTS: The population aged over 65 accounted for 38% (n=1193) of the 3178 adult implanted patients. The performance for mono- and disyllabic words in silence, the CAP scores and the APHAB questionnaire answers for ease of communication, background noise and reverberation were dramatically improved at one year post-implantation (P<0.0001 for each score) and remained stable between one and three years thereafter. The percentage improvement was similar across all age groups. The scores for loud-noise intolerance did not change after cochlear implantation in any age group. CONCLUSION: Cochlear implants improve hearing and communication in subjects aged 65 and over, with comparable efficiency to that achieved in younger subjects. Cochlear implantation should thus be proposed whenever hearing aids provide only limited benefit. However, between 2012 and 2016, cochlear implantation was given to less than 1% of the French population aged 65 and over with profound deafness.

Rehabilitation of telephone communication in cochlear-implanted adults.

OBJECTIVES: Telephone use correlates with quality of life, and is one of the most important expectations of cochlear implant candidates. The aim of the present study was to assess the benefit of a progressive intensive 18-session training program, conducted by telephone in cochlear implant recipients. MATERIAL AND METHODS: Nine cochlear-implanted adults underwent telerehabilitation focused on telephone use, with before-and-after assessment of: auditory performance, on Lafon monosyllabic words and MBAA sentences in quiet, cocktail-party noise and by phone; telephone use, on ad-hoc surveys and number of calls per week; and quality of life on ERSA and APHAB questionnaires. RESULTS: Before training, monosyllabic word comprehension was poorer by telephone than by direct voice (64±5.7% vs. 26±5.3%; P<0.05). After the 6-week training, there was improvement in the "note taking" telephone message task (85.0±3.7 vs. 50.0±9.0 out of 100; P<0.001), daily phone use (57.0±4.3 vs. 29±5.4 out of 100; P<0.0001), and number of calls in the week before assessment (0.0±0.0 vs. 11.0±3.0; P<0.0001). CONCLUSIONS: A progressive intensive training program by telephone improved phone use in the daily life of cochlear-implanted adults.

Intraoperative Conebeam CT for Assessment of Intracochlear Positioning of Electrode Arrays in Adult Recipients of Cochlear Implants.

BACKGROUND AND PURPOSE: Intraoperative conebeam CT has been introduced into the operating room and provides quick radiologic feedback. This study aimed to investigate its utility in the assessment of the positioning of the electrode array after cochlear implantation. MATERIALS AND METHODS: This was a retrospective study of 51 patients (65 ears) with intraoperative imaging by conebeam CT (O-arm) after cochlear implantation between 2013 and 2017. Correct placement into the cochlea was immediately identified. Positioning assessments were later analyzed with OsiriX software. RESULTS: Intraoperative imaging was quickly performed in all cases. No misplacement into the vestibule or semicircular canals was found. A foldover of the implanted array was identified in 1 patient. Secondary analysis by 2 raters showed excellent agreement on insertion depth angle (intraclass correlation = 0.96, P < .001) and length of insertion of the electrode array (intraclass correlation coefficient = 0.93, P = .04) measurements. The evaluation of the number of extracochlear electrodes was identical between the 2 raters in 78% of cases (Cohen κ = 0.55, P < .001). The scalar position was inconsistent between raters. When we compared O-arm and high-resolution CT images in 14 cases, the agreement was excellent for insertion depth angle (intraclass correlation coefficient = 0.97, P < .001) and insertion length (intraclass correlation coefficient = 0.98, P < .001), good for the number of extracochlear electrodes (Cohen κ = 0.63, P = .01), but moderate for the scalar position (Cohen κ = 0.59, P = .02). CONCLUSIONS: Intraoperative conebeam CT using the O-arm is a safe, rapid, easy, and reliable procedure to immediately identify a misplacement or foldover of an electrode array. The insertion depth angle, insertion length, and number of electrodes inserted can be accurately assessed.

Evaluation of the impact of hearing loss in adults: Validation of a quality of life questionnaire.

OBJECTIVES: The impact of hearing loss and of auditory rehabilitation (hearing aid, cochlear implant) on quality of life is a crucial issue. Commonly used questionnaires to assess quality of life in these patients (Nijmegen, APHAB, GBI) are time-consuming, difficult for patients to fill out, and show poor sensitivity to small improvements or deterioration. The objective of the present study was to validate a dedicated quality of life scale for hearing-impaired adults with or without auditory rehabilitation. MATERIAL AND METHODS: ERSA (Évaluation du Retentissement de la Surdité chez l'Adulte: Evaluation of the Impact of Hearing Loss in Adults) is a self-administered questionnaire. It is divided into 4 domains, each comprising 5 questions graded from 1 to 10. The questions are simple, and formulated so patients will answer according to how they feel at the actual time of the session. Test-retest reliability was measured in 38 patients. Internal coherence and validity against the APHAB questionnaire as gold standard and in relation to hearing performance were measured in 122 patients at auditory assessment. Sensitivity to change in hearing was measured in 36 cochlear implant patients, before and 6 or 12 months after implantation. RESULTS: Test-retest reliability was very satisfactory (ρ=0.88). Internal coherence was good for all questions. External validity, comparing ERSA to APHAB scores in the same non-implanted hearing-impaired patients, was good (ρ=0.52). Additionally, ERSA scores correlated with hearing performance in adverse conditions (monosyllabic words: ρ=0.22; sentences in noise: ρ=0.19). In patients tested before and after cochlear implantation, improvement in hearing performance in silence and in noise correlated with an improvement in ERSA score (ρ=0.37 to 0.59, depending on the test), but not to GBI score. CONCLUSION: The ERSA questionnaire is easy and quick to use, reliable, and sensitive to change in hearing performance after cochlear implantation.

Vagal and recurrent laryngeal nerves neuromonitoring during thyroidectomy and parathyroidectomy: A prospective study.

OBJECTIVES: The aim of the study was to stimulate the vagal and the recurrent laryngeal nerves during and after thyroidectomy or parathyroidectomy, to record muscle responses, interpret the electrophysiological modifications and identify prognostic factors for postoperative vocal fold mobility. PATIENTS AND METHODS: A prospective study monitored 151 vagal nerves and 144 recurrent laryngeal nerves in 114 patients. Seven patients (14 vagal nerves) underwent continuous monitoring via an automatic periodic stimulation (APS®) electrode. In 15 patients (21 vagal nerves), the stimulation threshold was studied. Muscle response was recorded on direct vagal and/or recurrent laryngeal nerve stimulation by a monopolar electrode or direct repeated stimulation via an electrode on the vagal nerve. In case of signal attenuation on the first operated side, surgery was not extended to the contralateral side. RESULTS: The vagal nerve stimulation checked inferior laryngeal nerve integrity and recurrent status, without risk of false negatives. The vagal nerve stimulation threshold, before and after dissection, that induced a muscle response of at least 100µV ranged from 0.1 to 0.8mA. Similarity between pre- and post-dissection responses to supramaximal stimulation, defined as 1mA, on the one hand, and between post-dissection vagal and laryngeal recurrent nerve responses on the other correlated with normal postoperative vocal cord mobility. Conversely, muscle response attenuation below 100µV and increased latency indicated a risk of vocal fold palsy. CONCLUSION: Vagal nerve stimulation allows suspicion or elimination of lesions on the inferior laryngeal nerve upstream of the stimulation point and detection of non-recurrent inferior laryngeal nerve. Intermittent monitoring assesses nerve function at the moment of stimulation, while continuous monitoring detects the first signs of nerve injury liable to induce postoperative recurrent nerve palsy. When total thyroidectomy is indicated, signal attenuation on the first operated side casts doubt on continuing surgery to the contralateral side in the same step.

Anatomical, functional and quality-of-life results for mastoid and epitympanic obliteration with bioactive glass s53p4: a prospective clinical study.

OBJECTIVE: To analyse the anatomical, functional and quality-of-life results when using bioactive glass in mastoid and epitympanic obliteration. DESIGN: Prospective clinical study. SETTING: Tertiary referral centre. PARTICIPANTS: Forty-one cases (39 patients) operated between May 2013 and January 2015. MAIN OUTCOME MEASURES: Anatomical results were evaluated by otomicroscopy 1 year after surgery and using imaging to detect residual disease. Functional results were studied by postoperative hearing gain. Quality of life was assessed with the Glasgow Benefit Inventory questionnaire and the success of surgery by a surgery-specific questionnaire. RESULTS: At 1 year, all patients presented a well-healed external auditory canal, with an intact tympanic membrane. In cases with cholesteatoma (n = 23), no recurrent retraction pockets or residual disease were observed on imaging studies. The overall air-bone gap closure was 7.7 ± 1.84 dB (mean ± se of the mean, P < 0.001, paired t-test). No significant differences were found on hearing results when comparing primary versus revision surgery, canal-wall-up versus canal-wall-down obliterations, type of tympanoplasty and presence of cholesteatoma (multifactor anova). The Glasgow Benefit Inventory improved with an average score of 28 and the success of surgery questionnaire showed a significant improvement in ear discharge and a moderate improvement in hearing and equilibrium. CONCLUSIONS: The use of bioactive glass for mastoid and epitympanic obliteration in canal-wall-down or canal-wall-up tympanoplasties is an effective procedure in both primary and revision surgery. The anatomical and functional results appear to be well correlated with patient experience and to the improvement in quality of life.

The pathophysiology of otosclerosis: Review of current research.

Otosclerosis is a complex disease of the human otic capsule with highest incidence in adult Caucasians. So far, many possible etiological factors like genetics, HLA, autoimmunity, viruses, inflammation, and hormones have been investigated but still the development of the disease remains unclear. Currently, the surgical replacement of stapes (stapedotomy) remains the best possible treatment option. In this review, we analyze different etiological factors studied so far in otosclerosis pathophysiology and discuss most recent findings and possible new research pathways.

[Cochlear implant in adults]. / Implants cochléaires chez l'adulte.

Cochlear implant in adults is a procedure, dedicated to rehabilitate severe to profound hearing loss. Because of technological progresses and their applications for signal strategies, new devices can improve hearing, even in noise conditions. Binaural stimulation, cochlear implant and hearing aid or bilateral cochlear implants are the best opportunities to access to better level of comprehension in all conditions and space localisation. By now minimally invasive surgery is possible to preserve residual hearing and use a double stimulation modality for the same ear: electrical for high frequencies and acoustic for low frequencies. In several conditions, cochlear implant is not possible due to cochlear nerve tumour or major malformations of the inner ear. In these cases, a brainstem implantation can be considered. Clinical data demonstrate that improvement in daily communication, for both cochlear and brainstem implants, is correlated with cerebral activation of auditory cortex.

Intraoperative laryngeal nerve monitoring during thyroidectomy and parathyroidectomy: A prospective study.

OBJECTIVES: The aim of this study was to stimulate the recurrent laryngeal nerve during thyroidectomy or parathyroidectomy and to record the muscle responses in an attempt to predict postoperative vocal fold mobility. PATIENTS AND METHODS: Intraoperative recurrent laryngeal nerve monitoring during general anaesthesia was performed by using an electrode-bearing endotracheal tube (nerve integrity monitor EMG endotracheal tube [Medtronic Xomed, Jacksonville, Flo, USA]). Two hundred and fifteen recurrent laryngeal nerves from 141 patients undergoing total thyroidectomy (n=74), hemithyroidectomy (n=63), or parathyroidectomy (n=4) were prospectively monitored. In each case, the muscle potential was recorded after stimulation of the recurrent laryngeal nerve by a monopolar probe. RESULTS: The nerve stimulation threshold before and after dissection that induced a muscle response of at least 100 µV ranged from 0.1 to 0.85 mA (mean 0.4 mA). The supramaximal stimulation intensity was defined as 1 mA. The amplitude of muscle response varied considerably from one patient to another, but the similarity of the muscle response at supramaximal intensity between pre- and postdissection and between postdissection at the proximal and distal exposed portions of the nerve was correlated with normal postoperative vocal fold function. Inversely, alteration of the muscle response indicated a considerable risk of recurrent laryngeal nerve palsy, but was not predictive of whether or not this lesion would be permanent. CONCLUSIONS: Recurrent laryngeal nerve monitoring with a system using surface electrodes is a simple, non-invasive technique that is just as sensitive as monitoring by intramuscular electrodes. Monitoring is helpful for initial nerve identification and is useful to determine nerve function during and after surgery, and to adapt the surgical strategy accordingly.

Hearing loss severity: impaired processing of formant transition duration.

Normal hearing listeners exploit the formant transition (FT) detection to identify place of articulation for stop consonants. Neuro-imaging studies revealed that short FT induced less cortical activation than long FT. To determine the ability of hearing impaired listeners to distinguish short and long formant transitions (FT) from vowels of the same duration, 84 mild to severe hearing impaired listeners and 5 normal hearing listeners were asked to detect 10 synthesized stimuli with long (200 ms) or short (40 ms) FT among 30 stimuli of the same duration without FT. Hearing impaired listeners were tested with and without hearing aids. The effect of the difficulty of the task (short/long FT) was analysed as a function of the hearing loss with and without hearing aids. Normal hearing listeners were able to detect every FT (short and long). For hearing impaired listeners, the detection of long FT was better than that of short ones irrespective of their degree of hearing loss. The use of hearing aids improved detection of both kinds of FT; however, the detection of long FT remained much better than the detection of the short ones. The length of FT modified the ability of hearing impaired patients to detect FT. Short FT had access to less cortical processing than long FT and cochlea damages enhanced this specific deficit in short FT brain processing. These findings help to understand the limit of deafness rehabilitation in the time domain and should be taken into account in future devices development.

Cochlear implantation and far-advanced otosclerosis.

OBJECTIVE: To evaluate results of cochlear implantation in patients with far-advanced otosclerosis. METHODS: Sixteen patients with far-advanced otosclerosis had undergone unilateral (n = 13) or bilateral (n = 3) cochlear implantation. Surgical difficulties, incidence of complications and postoperative benefit were analyzed. RESULTS: A full electrode insertion was achieved in all patients without surgical difficulties. All patients demonstrated excellent benefit of cochlear implantation. Binaural implantation still improves speech performances, compared to unilateral implantation. In case of residual cochlear function of one nonoperated side, a stapes surgery, performed during the same surgical time as cochlear implantation, can improve speech scores and restore bilateral hearing. Facial nerve stimulation occurred only in 1 patient. CONCLUSION: Cochlear implantation is the method of choice for rehabilitation of patients with otosclerosis, presenting profound or total hearing loss. Patients obtain excellent benefit with a low rate of complications.

[Performances and complications of cochlear implant in 134 adult patients implanted since 1990]. / Performances et complications de l'implant cochléaire chez 134 patients adultes implantés depuis 1990.

OBJECTIVE: The aim of this study was to analyse performance of cochlear implants in a retrospective series of adults with postlingually in order to search for predictive factors and identify complications. METHODS: Between 1990 and 2003, 134 adult patients were implanted: 129 patients on one side and 5 patients on both sides. Hearing benefit at 6, 12, 24 and 36 months and performance at 12 months were analyzed as function of the etiology, age at implantation, lipreading and speech coding strategy. RESULTS: Compared to performances before implantation, cochlear implants provided significant and rapid improvement at 6 months (p<0.0001). The results were not correlated with age at implantation, etiology or lipreading ability before implantation. Performances were worse in patients with meningitis (p<0.01), but the percentage of improvement was similar between the different etiologies. Major complications were rare: one case of regressive postoperative facial nerve weakness. CONCLUSION: Cochlear implants provide significant and rapid improvement, with low morbidity. Results are not correlated with age at implantation, etiology or lipreading ability.

[Beneficial effect of cochlear implants in the elderly]. / Bénéfice de l'implant cochléaire chez le sujet âgé.

OBJECTIVE: To evaluate the benefit of cochlear implantation in older adults aged 60 Years and over. METHODS: Fifty-six profoundly or totally hearing-impaired patients, aged 60 Years and over, were studied retrospectively. At the end of the preoperative evaluation, 28 patients received a cochlear implant. The mean age was 66 Years and the median follow-up was 22.5 Months. Speech perception scores before and after implantation were analyzed in order to evaluate the benefit of cochlear implantation. The speech perception score before implantation was compared to that of the non-implanted patients. RESULTS: There was a significant improvement of the dissyllabic words and sentences scores after implantation. The patients who are over 70 Years performed as well as those who are younger (between 60 and 70 Years). One patient developed a postoperative vertigo due a perilymphatic fistula. There was no flap-related problems. In the non-implanted group (mean age: 68 Years), 18 patients declined the cochlear device because they thought the subjective benefit of their hearing aid was sufficient and 5 patients declined because of surgical risk. The mean age, the cause and the duration of the deafness, and the speech perception scores were similar between implanted and non-implanted patients. CONCLUSION: This study demonstrates the beneficial effect of cochlear implantation in the elderly. These results suggest that a similar benefit could have been obtained in the patients who declined surgery. An early implantation could reduce the duration of the deafness and preserve binaural sound perception allowing increased performance in older people.

Temporal bone density measurements using CT in otosclerosis.

OBJECTIVE: To assess the bone density around the bony labyrinth in otosclerosis patients and to compare it to that of a control population. MATERIAL AND METHODS: This was a prospective case-control study. Ten patients with otosclerosis (mean age 42 years; range 24-55 years) and 33 control patients with vestibular schwannoma (mean age 46 years; range 20-71 years) were included. All patients underwent a clinical examination, audiometry and a CT scan comprising axial and coronal views of both temporal bones. In the otosclerosis group, audiometry showed unilateral involvement in six patients and bilateral hearing loss in four. The bone density was measured at the fissula ante fenestram (FAF) and at five other anatomical points on the bony labyrinth. RESULTS: In the control group, the bone density was similar at the six anatomical points. In the otosclerosis patients, the mean bone density at the FAF was lower than that in control patients (1649+/-99.1 vs 2049+/-13.4 HU; p < 0.01). For patients with FAF bone densities < 2000 HU, a correlation was observed between hearing threshold and FAF bone density. CONCLUSION: FAF bone density appears to be a good indicator of disease progression, and could serve as a follow-up and prognostic parameter.

[Na transport in the cochlea of mammals]. / Transports de Na dans la cochlée de mammifères.

Endolymph, the fluid that bathes the apical side of the inner ear sensory cells, is a K-rich and Na-poor fluid. In the cochlea, various epithelial transport systems involved in the transport of Na from the apical endolymphatic to the basolateral perilymphatic compartments have been identified: basolateral Na+, K(+)-ATPase, apical non selective cationic channels, Na+/H+ exchanger, and ENaC epithelial Na channel. These transporters may be involved in physiological and pathological processes in which endolymph Na concentration is high.

Local administration of antioxidants to the inner ear. Kinetics and distribution(1).

Round window (r.w.) administration of drugs involves the delivery of medication directly into the inner ear via the r.w. membrane, avoiding a systemic effect of the therapy. Earlier experimental studies suggest that a number of antioxidants and scavengers hold promise for ameliorating the tissue damaging capacity of reactive oxygen species in some acquired cochlear disorders. D-Methionine and thiourea are two small sulfur-containing molecules with an antioxidative and scavenging effect. The passage through the r.w. of radioactive D-methionine and thiourea administered by 1 h infusion to the r.w. was studied in a rat model. Levels of the tracers were measured in scala tympani perilymph (PLT) 17-254 min after r.w. administration. Both tracers pass the r.w. membrane readily. Peak levels were found in the earliest taken samples after the administration. The radioactivity in PLT of the basal turn reached a peak to about 1.5-1.9% of the irrigating medium radioactivity. Following the r.w. administration, the concentration of radioactive D-methionine and thiourea declined with a terminal half-life of 0.57 and 0.77 h, respectively. The distribution of the tracers at the cellular level was analyzed by autoradiography. The most intense expression was found in the lateral wall of the cochlea. It can be postulated that local delivery to the cochlea of D-methionine and thiourea via the r.w. gives high local concentrations of the substances in PLT in the basal turn.

Influence of trimetazidine on the synthesis of complex lipids in the heart and other target organs.

Trimetazidine exerts antianginal properties at the cellular level, without haemodynamic effect in clinical and experimental conditions. This cytoprotection was attributed to a decreased utilization of fatty acids for energy production, balanced by an increased incorporation in structural lipids. This study evaluated the influence of Trimetazidine on complex lipid synthesis from [2-(3)H] glycerol, in ventricular myocytes, isolated rat hearts and in vivo in the myocardium and several other tissues. In cardiomyocytes, Trimetazidine increased the synthesis of phosphatidyl-choline (+ 80%), phosphatidyl-ethanolamine (+ 210%), phosphatidyl-inositol (+ 250%) and cardiolipid (+ 100%). The common precursor diacylglycerol was also increased (+ 40%) whereas triacylglycerol was decreased (-70%). Similar results were obtained in isolated hearts with 10 microm Trimetazidine (phosphatidyl-choline + 60%, phosphatidyl-ethanolamine + 60%, phosphatidyl-inositol + 100% and cardiolipid + 50%), the last two phospholipids containing 85% of the radioactivity. At 1 microm, Trimetazidine still stimulated the phospholipid synthesis although the difference was found significant only in phosphatidyl-inositol and cardiolipid. In vivo studies (10 mg/kg per day for 7 days and 5 mg/kg, i.p. before the experiment) revealed significant changes in the intracellular lipid biosynthesis, with increased labelling of phospholipids and reduced incorporation of glycerol in nonphosphorous lipids. Trimetazidine increased the glycerol uptake from plasma to the other tissues (liver, cochlea, retina), resulting in an altered lipid synthesis. The anti-anginal properties of Trimetazidine involve a reorganisation of the glycerol-based lipid synthesis balance in cardiomyocytes, associated with an increased uptake of plasma glycerol that may contribute to explain the pharmacological properties reported in other organs.

H+,K+-ATPase is not involved in endolymph pH homeostasis.

In endolymph, the calculated electrochemical gradients suggest the presence of active transport of H+ and K+. The presence of H+,K+-ATPase, an active transporter that mediates the exchange of intracellular H+ for extracellular K+, was investigated using reverse transcription-polymerase chain reaction on rat microdissected inner ear tissues. Distal colon and kidney were used as positive controls. The two H+,K+-ATPase colonic or gastric isoforms were not detected in the rat cochlea and endolymphatic sac. This result suggests that H+,K+-ATPase is not involved in H+ and K+ endolymph homeostasis.

Purine and pyrimidine nucleotide-sensitive phospholipase A(2) in ampulla from frog semicircular canal.

This study was attempted to characterize pharmacologically the P2Y receptors triggering phospholipase A(2) (PLA(2)) activation in ampulla from frog semicircular canal. A microassay was developed to screen the abilities of UTP analogs to stimulate [(3)H]arachidonic acid release by labeled ampullas. At 26 degrees C UTP induced a dose-dependent and saturable increase of PLA(2) activity (apparent activation constant 1.3 +/- 0.4 microM, Hill coefficient 0.9 +/- 0.2, maximal stimulating factor 2.0 +/- 0.1). The rank order of potency of agonists for PLA(2) activation was UTP > or = UDP > adenosine 5'-O-(2-thiodiphosphate) = adenosine 5'-O-(3-thiotriphosphate) > or = ATP = 2-methylthio-ATP > or = ADP = diadenosine tetraphosphate > or = alpha,beta-methylene-ATP = CTP > 2' and 3'-O-(4-benzoylbenzoyl)-ATP > or = AMP = UMP >> uridine and adenosine. UTP- and 2-methylthio-ATP-induced PLA(2) activations were inhibited by U-73122, GF-109203X, and methyl arachidonyl fluorophosphate. Basal activity was stimulated by phorbol ester and epinephrine and reduced by vasotocin, isoproterenol, prostaglandin E(2), cAMP, and forskolin. H-89 restored the cAMP- and forskolin-inhibited PLA(2) activities. Results indicate that P2Y receptor-mediated PLA(2) stimulation requires phopholipase C and protein kinase C activations and basal activity is inhibited by agonist-stimulated cAMP-dependent mechanisms.

Location and function of the epithelial Na channel in the cochlea.

In the cochlea, endolymph is a K-rich and Na-poor fluid. The purpose of the present study was to check the presence and to assess the role of epithelial Na channel (ENaC) in this organ. alpha-, beta-, and gamma-ENaC subunit mRNA, and proteins were detected in rat cochlea by RT-PCR and Western blot. alpha-ENaC subunit mRNA was localized by in situ hybridization in both epithelial (stria vascularis, spiral prominence, spiral limbus) and nonepithelial structures (spiral ligament, spiral ganglion). The alpha-ENaC-positive tissues were also positive for beta-subunit mRNA (except spiral ganglion) or for gamma-subunit mRNA (spiral limbus, spiral ligament, and spiral ganglion), but the signals of beta- and gamma-subunits were weaker than those observed for alpha-subunit. In vivo, the endocochlear potential was recorded in guinea pigs under normoxic and hypoxic conditions after endolymphatic perfusion of ENaC inhibitors (amiloride, benzamil) dissolved either in K-rich or Na-rich solutions. ENaC inhibitors altered the endocochlear potential when Na-rich but not when K-rich solutions were perfused. In conclusion, ENaC subunits are expressed in epithelial and nonepithelial cochlear structures. One of its functions is probably to maintain the low concentration of Na in endolymph.