Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice / 神经科学通报·英文版

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 basilar membrane 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 cell'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 frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.

Prestin and Motility of the Cochlear Outer Hair Cell

The main objective of this study is to describe the role and function of prestin on cochlear amplification based on the relationship of electromotility and prestin in the outer hair cells (OHCs). After the finding of cochlear active process or amplification, OHCs have been received a lot of attention as a source of the cochlear amplification. In response to acoustic signals, the OHCs produce the receptor potentials resulting in changes in the length of the OHCs called electromotility. The electromotility originates within the lateral wall of the OHCs and relates to the unique structures of the OHCs. The OHC electromotility depends on particles of the lateral plasma membrane due to an area motor in the lateral plasma membrane. Recently, it has been reported that the electromotility requires a voltage-dependent membrane based motor protein, prestin. Prestin means fast in Italian. The presence of prestin is essential for cochlear amplification and electromotility. Prestin is a member of solute carrier 26 anion transporter family. Prestin is associated with the unique structure of the lateral wall of the OHCs. Prestin forms motor complexes with other proteins and lipids of the lateral wall sensing the transmembrane potential and generating force by changing its surface area. Recently, prestin knockout mice have been used to prove the presence of prestin. Prestin is required for electromotility of the OHCs and for cochlear amplification in normal hearing because targeted depletion of prestin in mice leads to loss of OHC electromotility and loss of hearing sensitivity up to 60 dB. In addition, recent studies have shown that the loss of cochlear amplification after intense noise exposure can result from damage to prestin and prestin involves in the process of aminoglycoside-induced apoptosis in OHCs. These show that prestin plays an important role in transducing apoptosis signals in response to antibiotics. Therefore, the presence of prestin is mandatory for cochlear active process and amplification in normal hearing.

The Influence of Sodium salicylate on the Expression of Na+ -K+ -2Cl- / 听力学及言语疾病杂志

Objective To investigate the different expression levels of Na+ - K+ - 2Cl- co- transporter NKCC1 mRNA in the cochlea of rats after sodium salicylate injection and to explore the mechanism underlying the change of outer hair cells, induced by different salicylate administration. Methods Twenty-four normal adult rats were randomly divided into four groups with six rats in each group. Rats in control group,did not recieve sodium sa-licylate injection. The other three groups were acute group,chronic group,and recovered group according to the dif-ferent doses of sodium salicylate. The fluorescence quantitative PCR method was used to detect the expression levels of NKCC1 mRNA in the rat cochleas of the four groups. Results NKCC1 mRNA was expressed in all of the four groups. After sodium salicylate injection, the expressions of NKCC1 mRNA in chronic and recovered group were higher than that in control group(P<0.05). While the expression of NKCC1 mRNA in acute group was lower than that in control group(P(0. 05). Conclusion The expression of NKCC1 mRNA in the normal cochlea indicates that NKCC1 may play an important role in the maintenance of Cl- in the endolymph of the cochlea. The alteration of NKCC1 mRNA expression caused by sodium salicylate injection may lead to the change of the outer hair cell electro-motility.

The Distribution of Prestin on the Whole Basolateral Surface of Outer Hair Cells / 听力学及言语疾病杂志

Objective The prestin,a motor protein responsible for outer hair cell(OHC)electromotility,is expressed on the OHC surface.Previous experiments revealed that OHC electromotility and its associated nonlinear capacitance was mainly located at the OHC lateral wall and was absent at the apical cuticular plate and the basal nucleus pole.Immunofluorescent staining for prestin failed to demonstrate the prestin expression at the OHC basal ends in whole-mount preparation of the organ of Corti.The aim of this study is to investigate the distribution of prestin at OHC.Methods In this experiment,the localization of prestin protein in single dissociated OHCs from cochlea of normal mouse,rat and guinea pig,were examined by immunofluorescent staining and confocal microscopy.Results We found that prestin was uniformly expressed on the OHC basolateral surface,including its basal pole.No staining was observed on the cuticular plate and stereocilia.The OHC lateral wall had a trilaminate organization and was composed of the plasma membrane,cortical lattice,and subsurface cisternae.By with co-staining with a membrane marker di-8-ANEPPS,prestin-labeling was found locating at the outer layer of the OHC lateral wall.Further separating the plasma membrane from the underlying subsurface cisternae,using a hypotonic extracellular solution,prestin-labeling was shown locating at the plasma membrane instead of the subsurface cisternae.Conclusion The data revealed that prestin is expressed in the plasma membrane on the whole OHC basolateral surface.

The Influence of Sodium Salicylate on the Expression of Na~+-K~+-2Cl~- / 听力学及言语疾病杂志

Objective To investigate the different expression levels of Na+-K+-2Cl-co-transporter NKCC1 mRNA in the cochlea of rats after sodium salicylate injection and to explore the mechanism underlying the change of outer hair cells,induced by different salicylate administration.Methods Twenty-four normal adult rats were randomly divided into four groups with six rats in each group. Rats in control group,did not recieve sodium salicylate injection. The other three groups were acute group,chronic group,and recovered group according to the different doses of sodium salicylate.The fluorescence quantitative PCR method was used to detect the expression levels of NKCC1 mRNA in the rat cochleas of the four groups.Results NKCC1 mRNA was expressed in all of the four groups.After sodium salicylate injection,the expressions of NKCC1 mRNA in chronic and recovered group were higher than that in control group(P