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Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice

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Neuroscience Bulletin 2022年第7期38卷 769-784页

作者： Jie Li Shuang Liu Chenmeng Song Tong Zhu Zhikai Zhao Wenzhi Sun Yi Wang Lei Song Wei Xiong School of Life Sciences Tsinghua UniversityBeijing 100084China IDG/MeGovern Institute for Brain Research at Tsinghua University Tsinghua UniversityBeijing 100084China Chinese Institute for Brain Research Beijing 102206China School of Basic Medical Sciences Capital Medical UniversityBeijing 100069China Department of Otolaryngology Head and Neck SurgeryShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Ear Institute Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases Shanghai 20001lChina

In mammals,the piezoelectric protein,Prestin,endows the Outer hair cells(OHCs)with electromotility(eM),which confers the capacity to change cellular length in response to alterations in membrane potential.Together with basilarmembrane resonance and possible stereociliary motility,Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity.However,it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cel's low-pass features.The low-pass_property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech.In this study,we examined the role of Prestin in sensing broad-range frequencies(4-80 kHz)in mice that use ultrasonic hearing and vocalization(to>100 kHz)for social communication.The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies>40 kHz.Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks,similar to control mice.Ex vivo cochlear Ca2+imaging experiments demonstrated that without Prestin,the OHCs still exhibit ultrahigh-frequency transduction,which in contrast,can be abolished by a universal cation channel blocker,Gadolinium.In vivo salicylate treatment disrupts hearing at frequencies40 kHz.These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction,which does not require Prestin.

关键词： Prestin PIEZO2 Ultrahigh-frequency hearing Electromotility Outer hair cells

Effect of age on click-evoked otoacoustic emission A systematic review

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Neural Regeneration Research 2012年第11期7卷 853-861页

作者： Jinfeng Liu Ningyu Wang Department of Otorhinolaryngology Head and Neck Surgery Beijing Chaoyang HospitalCapital Medical UniversityCollege of OtolaryngologyCapital Medical UniversityKey Laboratory of Otolaryngology Head and Neck SurgeryBeijing 100020China

OBJECTIVE：The aims of this study were to investigate the changes of the total intensity of transient evoked otoacoustic emission（TEOAE） and signal-to-noise ratio in various frequency bands as a function of aging,and to explore the role of age-related decline of cochlear Outer hair cells.DATA SOURCES：The literature was searched using the PubMed database using ＇transient-evoked otoacoustic emissions＇ as a keyword.Articles were limited as follows：Species was ＇Humans＇;languages were ＇English and Chinese＇;publication date between 1990-01-01 and 2010-12-31.The references of the found were also searched to obtain additional articles.DATA SELECTION：Inclusion criteria：（1） Articles should involve the total TEOAE level or signal-to-noise ratio.（2） The measurement and analysis system used was Otodynamics ILO analysis system（ILO88,ILO92,ILO96 or ILO292）.（3） Studies involved groups of greater than 10 subjects and TEOAE results were from normally hearing ears.（4） If more papers from the same author or laboratory analyzed the same subjects,only one was used.MAIN OUTCOME MEASURES：The correlations of the age scale with the total level and signal-to-noise ratio of TEOAE was determined,respectively.RESULTS：（1） TEOAE total level gradually increased until 2 months of age,and then decreased with increasing age.Significant negative correlations between total TEOAE level and age were found（r =-0.885,P = 0.000）.（2） The most rapid decrease of TEOAE amplitude occurred at 1 year old.The total TEOAE level decreased about 4.25 dB SPL between 2 months to 1 year old,then about 0.26-0.52 dB SPL from 1 year to 10 years old,about 0.23 dB SPL from 11 years to 25 years old,and about 0.14 dB SPL from 26 years to 60 years old.（3） The signal-to-noise ratio in the frequency bands centered at 1.5,2,3 and 4 kHz decreased with increasing age after 2 months of age.Significant negative correlations between the signal-to-noise ratio and age were found for frequency bands ranging from 1.5 kHz to 4 kHz,with the highest correlations at 4 kHz（r =-0.890,P 〈 0.01）,t

关键词： age transient-evoked otoacoustic emission signal-to-noise ratio Outer hair cells meta-analysis

Zinc-finger protein A20 protects hair cells from damage made by high-power microwave

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Journal of Bio-X Research 2019年第3期2卷 132-139页

作者： Feng Tang Xiaoling Chen Lifeng Jia Hai Li Jingya Li Wei Yuan Department of Otolaryngology The First Hospital Affiliated to the Third Military Medical University(Southwest Hospital)ChongqingChina

Inner ear hair cells are important for maintaining hearing.Irreversible damage to hair cells is an important cause of sensorineural deafness.Electromagnetic radiation,especially high-power microwave,is an important threat to human health in modern society and war.However,it is not clear whether high-power microwave has an effect on cochlea hair cells.This study aimed to assess the effects of high-power microwave on cochlear hair cells in guinea pigs,and investigate the potential protection of these cells against high-power microwave-induced damage by recombinant adenovirus A20.Based on experimental results,a 65 W/cm^(2) irradiation density applied to guinea pigs in this study to establish a high-power microwave inner ear injury model.In addition,pAdEeay-1/A20 was injected via a round window into experimental guinea pig cochlea,whereas artificial perilymph was injected into the control group.Auditory function was assessed by testing the auditory brainstem response threshold,and damage to cochlear hair cells was investigated by cell counting and scanning electron microscopy observations of the basilar membrane.Inner ear injury was observed 6 hours after 65 W/cm^( 2 ) of irradiation and the auditory brainstem response threshold was significantly higher in the irradiation group(Phair cells,which exhibited remarkable damage and the presence of several unknown spherical substances.Auditory brainstem response threshold was decreased in the pAdEeay-1/A20 group compared with the artificial perilymph group;moreover,damage to hair cells was milder in the pAdEeay-1/A20 group compared with the control group(Phair cells,as well as hearing loss with prolonged exposure and/or high dosage.In this regard,65 W/cm^( 2 ) of irradiation for 6 hours is a reliable target dose for obser

关键词： cochlea zinc finger protein A20 high power microwave inner hair cells Outer hair cells inner ear adenovirus microwave irradiation

Characterization of spontaneous otoacoustic emissions in 2–4 day old neonates with respect to gender and ear

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Neural Regeneration Research 2009年第1期4卷 67-71页

作者： Jinfeng Liu Baoyu Shi Ningyu Wang Jinlan Li Department of Otorhinolaryngology Head and Neck Surgery Beijing Chaoyang Hospital Capital Medical University Capital University of Medical Sciences School of Otolaryngology Key Laboratory of Otolaryngology Head and Neck Surgery (Capital Medical University) Ministry of Education Beijing 100020 China

BACKGROUND： Spontaneous otoacoustic emissions （SOAEs） are regarded as a valuable audio- metric parameter that objectively reflects the function of Outer hair cells （OHCs）. Many studies have reported that the incidence of SOAEs in adults is less than 50%. Therefore, measurement of SOAEs may be of little value to clinical examinations. However, the incidence of SOAEs in infants and neonates is higher than in adults. OBJECTIVE： To analyze the basic characteristics of SOAEs in 2–4 day old neonates, and to demonstrate the difference in OHC function between sexes and ears. DESIGN, TIME AND SETTING： Neurophysiological contrast study, performed in the Department of Neonates, Beijing Chaoyang Hospital, Capital Medical University, between December 2007 and August 2008. PARTICIPANTS： A total of 112 newborns （224 ears） consisting of 59 females and 53 males were included in this study. METHODS： The probe was adapted and embedded in the neonate external auditory canal with a foam rubber earplug after checking and clearing up the outer ear canal. The presence of SOAEs was determined when the signal amplitude had a clear peak exceeding –30 dB, or was 3 dB above the noise floor. MAIN OUTCOME MEASURES： The incidence of SOAEs, the number of SOAE signal peaks, and the maximal tension of SOAEs. RESULTS： The incidence in females （79.7%） was higher than males （76.4%）（P 〉 0.05）, and the incidence in right ears （86.6%） was higher than in left ears （69.6%）（P 〈 0.05）. There were no significant difference in the number of SOAE peaks between females and males （4.49 vs. 4.28）, or between right ears and left ears （4.62 vs. 4.12）（P 〉 0.05）. The mean maximum SOAE level per ear in females （–3.29 ± 9.28） dB sound pressure level （SPL） was slightly higher than that in males （–3.91 ± 9.14） dB SPL （P 〉 0.05）. Also, the mean maximum SOAE level in right ears （–2.03 ± 9.11） dB SPL was higher than in left ears （–5.50 ± 9.65） dB SPL （P 〈 0.05）. The maximum SOAE level showed a positive correlation with maximum SOAE number in emitting ears （r

关键词： spontaneous otoacoustic emission neonates auditory screening Outer hair cells

Measurement of Ca^(2+) Flow in Cochlear cells Using Non-Invasive Micro-Test Technique

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Journal of Otology 2010年第2期5卷 90-96页

作者： CHEN Shi-qin YU Ning YE Sheng-nan YANG Shi-ming ZHAI Suo-qiang Department of Otolaryngology Head and Neck Surgery Oto-Neurobiology CentreInstitute of OtolaryngologyChinese PLA General HospitalBeijing 100853China Department of Otolaryngology Affiliated First HospitalFujian Medical UniversityFuzhou 350005China

Objective To test Calcium ion(Ca2+) flow at the head and end of Outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in isolated OHCs in adult guinea pigs.Results Four types of Ca2+ transport were identified in OHCs on basilar membrane tissue fragments:influx at the head of with efflux at the bottom(type 1):efflux at the head of OHCs with influx at the bottom(type 2);influx at the both head and bottom(type 3);and efflux at the both head and bottom(type 4).However,only type 1 and type 3 of Ca2+ ion transport were detected in the cochlea.We propose that Ca2+ ion transport exists in adult guinea pig cochlear OHCs in resting state and is variable.Ca2 + flow in OHC can be inhibited by Nimodipine in resting state.

关键词： Guinea pig Outer hair cells Ca2+ ion non-invasive micro-test technique nimodipine.

Prestin forms tetramer with each subunit being mechanically independent

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Journal of Otology 2009年第2期4卷 86-97页

作者： WANG Xiang 1, GUO Wei-wei 2, HE David Zhi-Zhou1, YANG Shi-Ming 2 1 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA 2 Institute of Otolaryngology, Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853 Department of Biomedical Sciences Creighton University School of Medicine Omaha NE 68178 USA Institute of Otolaryngology Department of Otolaryngology Head and Neck Surgery Chinese PLA General Hospital Beijing 100853

Prestin is the motor protein of cochlear Outer hair cells （OHCs）. It is able to perform rapid and reciprocal electromechanical conversion that underlies OHC electromotility. Due to the inadequate size of a single prestin molecule to form the2 nm intramembraneous protein particles （IMPs） in the OHC lateral membrane （LM）, the possibility of prestin oligomerization has been proposed. It has been suggested that prestin molecules form highorder oligomers, most likely as the tetramer, in heterologous systems. In OHCs, however, the oligomeric structure of prestin remains unclear. Here we calculated the prestin-related charge density in both gerbil and guinea pig OHCs through measuring their nonlinear capacitance （NLC） and LM surface area, showing that the average charge density （22, 608 μm-2 in gerbils; 19, 460 μm-2 in guinea pigs） is statistically 4 times the average density of IMPs （5,686 μm-2 in gerbils; 5, 000 μm-2 in guinea pigs）. This suggests that each IMP contains four prestin molecules based upon the notion that each prestin transfers a single elementary charge, implying that prestin forms tetramers in OHCs. To determine whether the prestin tetramer functions as a mechanical unit, we subsequently compared the slope factors （α） of electromotility and NLC simultaneously measured from the same OHC, showing that the α values of the two are statistically the same. This suggests that each prestin molecule in the tetramer is mechanically independent and equally contributes to OHC electromotility.

关键词： Prestin oligomer Outer hair cells electromotility nonlinear capacitance gerbil