scholarly journals Effects of SERCA and PMCA inhibitors on the survival of rat cochlear hair cells during ischemia in vitro

2008 ◽  
pp. 631-638
Author(s):  
N Amarjargal ◽  
B Mazurek ◽  
H Haupt ◽  
N Andreeva ◽  
J Fuchs ◽  
...  
Keyword(s):  
Hair Cells ◽  
Smooth Endoplasmic Reticulum ◽  
Cyclopiazonic Acid ◽  
Significant Loss ◽  
Outer Hair Cells ◽  
Calcium Atpase ◽  
Dependent Manner ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell

An important mechanism underlying cochlear hair cell (HC) susceptibility to hypoxia/ischemia is the influx of Ca2+. Two main ATP-dependent mechanisms contribute to maintaining low Ca2+ levels: uptake of Ca2+ into intracellular stores via smooth endoplasmic reticulum calcium ATPase (SERCA) and extrusion of Ca2+ via plasma membrane calcium ATPase (PMCA). The effects of the SERCA inhibitors thapsigargin (10 nM-10 µM) and cyclopiazonic acid (CPA; 10-50 µM) and of the PMCA blockers eosin (1.5-10 µM) and o-vanadate (1-5 mM) on inner and outer hair cells (IHCs/OHCs) were examined in normoxia and ischemia using an in vitro model of the newborn rat cochlea. Exposure of the cultures to ischemia resulted in a significant loss of HCs. Thapsigargin and CPA had no effect. Eosin decreased the numbers of IHCs and OHCs by up to 25 % in normoxia and significantly aggravated the ischemia-induced damage to IHCs at 5 and 10 µM and to OHCs at 10 µM. o-Vanadate had no effect on IHC and OHC counts in normoxia, but aggravated the ischemiainduced HC loss in a dose-dependent manner. The effects of eosin and o-vanadate indicate that PMCA has an important role to play in protecting the HCs from ischemic cell death.

scholarly journals Olivocochlear suppression of outer hair cells in vivo: evidence for combined action of BK and SK2 channels throughout the cochlea

2013 ◽  
Vol 109 (6) ◽  
pp. 1525-1534 ◽  
Author(s):  
Stéphane F. Maison ◽  
Sonja J. Pyott ◽  
Andrea L. Meredith ◽  
M. Charles Liberman
Keyword(s):  
Hair Cells ◽  
In Vitro Study ◽  
Bk Channels ◽  
Outer Hair Cells ◽  
Cochlear Hair Cells ◽  
Α Subunit ◽  
Combined Action ◽  
Cholinergic Effects

Cholinergic inhibition of cochlear hair cells via olivocochlear (OC)-efferent feedback is mediated by Ca2+ entry through α9-/α10-nicotinic receptors, but the nature of the K+ channels activated by this Ca2+ entry has been debated (Yoshida N, Hequembourg SJ, Atencio CA, Rosowski JJ, Liberman MC. J Neurophysiol 85: 84–88, 2001). A recent in vitro study (Wersinger E, McLean WJ, Fuchs PA, Pyott SJ. PLoS One 5: e13836, 2010) suggests that small-conductance (SK2) channels mediate cholinergic effects in the apical turn, whereas large-conductance (BK) channels mediate basal turn effects. Here, we measure, as a function of cochlear frequency, the magnitude of BK and SK2 expression in outer hair cells and the strength of in vivo OC suppression in BK+/+ mice vs. BK−/− lacking the obligatory α-subunit (Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. J Biol Chem 279: 36746–36752, 2004). Except at the extreme apical tip, we see immunostaining for both BK and SK2 in BK+/+. Correspondingly, at all testable frequencies (8–45 kHz), we see evidence for both SK2 and BK contributions to OC effects evoked by electrically stimulating the OC bundle: OC-mediated suppression was reduced, but not eliminated, at all frequencies in the BK−/− ears. The suppression remaining in BK nulls was blocked by strychnine, suggesting involvement of α9-/α10-cholinergic receptors, coupled to activation of the remaining SK2 channels.

Cochlear Bone Erosion: Effects on Cochlear Hair Cells

1991 ◽  
Vol 100 (12) ◽  
pp. 1015-1019 ◽  
Author(s):  
Michael D. McGinn ◽  
Richard A. Chole
Keyword(s):  
Hair Cells ◽  
Bone Erosion ◽  
Significant Loss ◽  
Outer Hair Cells ◽  
Stage Iii ◽  
Cochlear Hair Cells ◽  
Basal Turn ◽  
Normal Controls ◽  
Experimentally Induced

Cochleae from gerbils with normal middle ears were compared with cochleae from gerbils with experimentally induced cholesteatomas that were in contact with the cochlear wall (stage III cholesteatomas). Cochleae from gerbils with stage III cholesteatomas were further divided into two groups: one without erosion of cochlear bone, and one with cholesteatoma-induced bone erosion but without cochlear fistulae. The cochleae with bone erosion showed significant loss of outer hair cells in the middle and apical turns, but not in the basal turn. The cochleae with stage III cholesteatomas but without bone erosion did not differ from normal controls. These results suggest that an ototoxic agent, involved in the process of bone erosion, acts through the bony cochlear wall.

Cochlear Hair Cell Stereocilia Loss in LP/J Mice with Bone Dysplasia of the Middle Ear

1989 ◽  
Vol 98 (6) ◽  
pp. 461-465 ◽  
Author(s):  
Richard A. Chole ◽  
Maggie Chiu
Keyword(s):  
Hair Cell ◽  
Middle Ear ◽  
Hair Cells ◽  
Inbred Mice ◽  
Bone Dysplasia ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Cochlear Hair Cells ◽  
Inner Hair Cells ◽  
Cochlear Hair Cell

LP/J inbred mice spontaneously develop bony lesions of the middle ear and otic capsule that are similar to those of human otosclerosis and tympanosclerosis. These mice also have progressive loss of hearing due to cochlear hair cell loss. The purpose of this study was to describe quantitatively the deterioration and loss of cochlear hair cells to serve as a basis for future experiments attempting to alter the course of this disorder. Cochleas from 37 LP/J inbred mice were examined by scanning electron microscopy. The stereocilia loss in the cochlea was evident as early as 15 weeks of age and progressed from the basal turn to the apex. Outer hair cells were affected more than inner hair cells. As outer hair cells deteriorated we observed fusion, bending, and breakage of stereocilia. There were no apparent differences in the mode of deterioration among the three rows of outer hair cells. Stereocilia fusion of inner hair cells occurred at an older age, and giant, elongated stereocilia were found in some of the animals.

scholarly journals Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell-Derived NeuronsIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Niliksha Gunewardene ◽  
Duncan Crombie ◽  
Mirella Dottori ◽  
Bryony A. Nayagam
Keyword(s):  
Hair Cells ◽  
Early Stage ◽  
Induced Pluripotent Stem Cell ◽  
Outer Hair Cells ◽  
Hesc Line ◽  
Auditory Neuron ◽  
Cochlear Hair Cells ◽  
Neural Processes ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) may serve as an autologous source of replacement neurons in the injured cochlea, if they can be successfully differentiated and reconnected with residual elements in the damaged auditory system. Here, we explored the potential of hiPSC-derived neurons to innervate early postnatal hair cells, using establishedin vitroassays. We compared two hiPSC lines against a well-characterized hESC line. After ten days’ coculturein vitro, hiPSC-derived neural processes contacted inner and outer hair cells in whole cochlear explant cultures. Neural processes from hiPSC-derived neurons also made contact with hair cells in denervated sensory epithelia explants and expressed synapsin at these points of contact. Interestingly, hiPSC-derived neurons cocultured with hair cells at an early stage of differentiation formed synapses with a higher number of hair cells, compared to hiPSC-derived neurons cocultured at a later stage of differentiation. Notable differences in the innervation potentials of the hiPSC-derived neurons were also observed and variations existed between the hiPSC lines in their innervation efficiencies. Collectively, these data illustrate the promise of hiPSCs for auditory neuron replacement and highlight the need to develop methods to mitigate variabilities observed amongst hiPSC lines, in order to achieve reliable clinical improvements for patients.

scholarly journals Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel–like proteins

2012 ◽  
Vol 141 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Kyunghee X. Kim ◽  
Robert Fettiplace
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Current Amplitude ◽  
Wild Type ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Channel Current ◽  
Transmembrane Channel ◽  
Sound Detection

Vibration of the stereociliary bundles activates calcium-permeable mechanotransducer (MT) channels to initiate sound detection in cochlear hair cells. Different regions of the cochlea respond preferentially to different acoustic frequencies, with variation in the unitary conductance of the MT channels contributing to this tonotopic organization. Although the molecular identity of the MT channel remains uncertain, two members of the transmembrane channel–like family, Tmc1 and Tmc2, are crucial to hair cell mechanotransduction. We measured MT channel current amplitude and Ca2+ permeability along the cochlea’s longitudinal (tonotopic) axis during postnatal development of wild-type mice and mice lacking Tmc1 (Tmc1−/−) or Tmc2 (Tmc2−/−). In wild-type mice older than postnatal day (P) 4, MT current amplitude increased ∼1.5-fold from cochlear apex to base in outer hair cells (OHCs) but showed little change in inner hair cells (IHCs), a pattern apparent in mutant mice during the first postnatal week. After P7, the OHC MT current in Tmc1−/− (dn) mice declined to zero, consistent with their deafness phenotype. In wild-type mice before P6, the relative Ca2+ permeability, PCa, of the OHC MT channel decreased from cochlear apex to base. This gradient in PCa was not apparent in IHCs and disappeared after P7 in OHCs. In Tmc1−/− mice, PCa in basal OHCs was larger than that in wild-type mice (to equal that of apical OHCs), whereas in Tmc2−/−, PCa in apical and basal OHCs and IHCs was decreased compared with that in wild-type mice. We postulate that differences in Ca2+ permeability reflect different subunit compositions of the MT channel determined by expression of Tmc1 and Tmc2, with the latter conferring higher PCa in IHCs and immature apical OHCs. Changes in PCa with maturation are consistent with a developmental decrease in abundance of Tmc2 in OHCs but not in IHCs.

Pengaruh sisplatin dosis tinggi terhadap penurunan fungsi sel rambut luar koklea

2013 ◽  
Vol 40 (2) ◽  
Author(s):  
Asti Kristianti ◽  
Teti Madiadipoera ◽  
Bogi Soeseno
Keyword(s):  
Hair Cells ◽  
Malignant Neoplasm ◽  
Otoacoustic Emission ◽  
Outer Hair Cells ◽  
High Dose ◽  
Distortion Product Otoacoustic Emission ◽  
Inclusion Criteria ◽  
Cochlear Hair Cells ◽  
Distortion Product ◽  
Bilateral Sensorineural Hearing Loss

Background: Chemotherapy is worldwide used nowadays, and its toxicity still remain a problemespecially toxicity to the ear (ototoxicity). Cisplatin (cis-diamminedichloroplatinum) is one of themost commonly used chemotherapy and highly potent in treating epithelial malignancies. Ototoxicitycaused by cisplatin is irreversible, progressive, bilateral, sensorineural hearing loss especially on highfrequency (4-8 KHz) accompanied by tinnitus. Purpose: To observe the cochlear outer hair cells damagein malignancies patients treated with cisplatin. Methods: This study is an observational analytic studywith prospective design to determine the influence of high dose cisplatin on cochlear outer hair cellsfunction. The research was carried out at the ENT-HNS Department, Hasan Sadikin General HospitalBandung, from November 2007 until June 2008. Audiometry, tympanometry, and distortion productotoacoustic emission (DPOAE) examinations were conducted before chemotherapy and DPOAE, andtimpanometry was again measured three days after first and second cycles of cisplatin administration. McNemar test was performed to calculate the effects of high-dose cisplatin to the cochlear outer haircells function. To compare pre and post-cisplatin on alteration of cochlear hair cells function, Wilcoxontest was used. Results: In this study 60 ears from 30 subjects that meet the inclusion criteria, consistedof 25 man (83.3%) and 5 women (16.7%). The prevalence of damaged cochlear outer hair cells were63% at first cycle and 70% at second cycle of cisplatin administration. The decline of cochlear outerhair cells function was significant (p<0.001). Conclusion: High-dose cisplatin decreases cochlear outerhair cells function in patients with malignant neoplasm. Abstrak : Latar belakang: Kemoterapi sekarang rutin digunakan secara klinis di seluruh dunia. Sejalan denganhal tersebut toksisitas kemoterapi, khususnya terhadap telinga saat ini menjadi perhatian. Sisplatin(cis-diamminedichloroplatinum) adalah salah satu obat kemoterapi yang paling banyak digunakandan paling manjur untuk terapi keganasan epitelial. Efek ototoksik sisplatin yaitu terjadi gangguandengar sensorineural yang irreversible, progresif, bilateral pada frekuensi tinggi (4-8 kHz), dan disertaidengan tinitus. Tujuan: Untuk menilai penurunan fungsi sel rambut luar koklea pada penderita tumorganas sesudah pemberian sisplatin dosis tinggi dengan menggunakan DPOAE. Metode: Studi analitikobservasional dengan rancangan prospektif di Bagian IK. THT-KL RS. Hasan Sadikin Bandung mulaibulan November 2007 sampai dengan Juni 2008. Pada penelitian ini dilakukan pemeriksaan audiometrinada murni, timpanometri, dan distortion product otoacoustic emission (DPOAE) prakemoterapi, kemudianDPOAE dan timpanometri diulang tiga hari sesudah siklus pertama dan kedua kemoterapi sisplatin. Datayang diperoleh diuji dengan uji McNemar dan uji Wilcoxon. Hasil: Dari penelitian didapat 60 telingadari 30 subjek penelitian yang memenuhi kriteria inklusi yang terdiri dari 25 laki-laki (83,3%) dan 5perempuan (16,7%). Insidens penurunan fungsi sel rambut luar koklea sebesar 63% (38 kasus) sesudahsiklus pertama dan 70% (42 kasus) sesudah siklus kedua. Hubungan penurunan fungsi sel rambut luarkoklea memberikan nilai yang sangat bermakna sejak pemberian siklus pertama (p<0,001). Kesimpulan:Pemberian sisplatin dosis tinggi pada penderita tumor ganas menyebabkan penurunan fungsi sel rambutluar koklea.Kata kunci: kemoterapi, sisplatin dosis tinggi, sel rambut luar koklea.

scholarly journals Effects of cochlear hair cell ablation on spatial learning/memory

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Z. Jason Qian ◽  
Anthony J. Ricci
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Spatial Learning ◽  
Hair Cells ◽  
Noise Exposure ◽  
Memory Errors ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Cell Ablation ◽  
Spatial Learning Memory

AbstractCurrent clinical interest lies in the relationship between hearing loss and cognitive impairment. Previous work demonstrated that noise exposure, a common cause of sensorineural hearing loss (SNHL), leads to cognitive impairments in mice. However, in noise-induced models, it is difficult to distinguish the effects of noise trauma from subsequent SNHL on central processes. Here, we use cochlear hair cell ablation to isolate the effects of SNHL. Cochlear hair cells were conditionally and selectively ablated in mature, transgenic mice where the human diphtheria toxin (DT) receptor was expressed behind the hair-cell specific Pou4f3 promoter. Due to higher Pou4f3 expression in cochlear hair cells than vestibular hair cells, administration of a low dose of DT caused profound SNHL without vestibular dysfunction and had no effect on wild-type (WT) littermates. Spatial learning/memory was assayed using an automated radial 8-arm maze (RAM), where mice were trained to find food rewards over a 14-day period. The number of working memory errors (WME) and reference memory errors (RME) per training day were recorded. All animals were injected with DT during P30–60 and underwent the RAM assay during P90–120. SNHL animals committed more WME and RME than WT animals, demonstrating that isolated SNHL affected cognitive function. Duration of SNHL (60 versus 90 days post DT injection) had no effect on RAM performance. However, younger age of acquired SNHL (DT on P30 versus P60) was associated with fewer WME. This describes the previously undocumented effect of isolated SNHL on cognitive processes that do not directly rely on auditory sensory input.

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 557-566 ◽  
Author(s):  
T. Self ◽  
M. Mahony ◽  
J. Fleming ◽  
J. Walsh ◽  
S.D. Brown ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Usher Syndrome ◽  
Orthologous Gene ◽  
Cell Development ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Show Evidence ◽  
Myosin Viia ◽  
And Function

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

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