online © ML Comm REVIEW Korean J Audiol 2011;15:101-106 pISSN 2092-9862 / eISSN 2093-3797 Prestin and Motility of the Cochlear Outer Hair Cell Chul-Hee Choi Department of Audiology and Speech-Language Pathology and Research Institute of Biomimetic Sensory Control, College of Medical Sciences, Catholic University of Daegu, Gyeongsan, Korea The main objective of this study is to describe the role and function of prestin on cochlear am- plification 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 electro- motility. 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 report- ed that the electromotility requires a voltage-dependent membrane based motor protein, pres- tin. 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 Received November 17, 2011 associated with the unique structure of the lateral wall of the OHCs. Prestin forms motor Revised December 8, 2011 complexes with other proteins and lipids of the lateral wall sensing the transmembrane poten- Accepted December 9, 2011 tial and generating force by changing its surface area. Recently, prestin knockout mice have Address for correspondence been used to prove the presence of prestin. Prestin is required for electromotility of the OHCs Chul-Hee Choi, PhD and for cochlear amplification in normal hearing because targeted depletion of prestin in mice Department of Audiology and leads to loss of OHC electromotility and loss of hearing sensitivity up to 60 dB. In addition, re- Speech-Language Pathology and cent studies have shown that the loss of cochlear amplification after intense noise exposure Research Institute of Biomimetic can result from damage to prestin and prestin involves in the process of aminoglycoside-in- Sensory Control, College of Medical duced apoptosis in OHCs. These show that prestin plays an important role in transducing apop- Sciences, Catholic University tosis signals in response to antibiotics. Therefore, the presence of prestin is mandatory for co- of Daegu, Hayang-eup, chlear active process and amplification in normal hearing. 13-3 Hayang-ro, Gyeongsan ; : 712-702, Korea Korean J Audiol 2011 15 101-106 Tel +82-53-850-3185 KEY WORDS: Outer hair cells (OHCs) · Electromotility · Prestin · Cochlear amplification · OHC Fax +82-53-850-3383 length · Noise-induced hearing loss · Ototoxicity. E-mail [email protected] Introduction age-dependent membrane based motor protein, prestin which is a member of solute carrier (SLC) 26 anion transporter fam- Hearing sensitivity in normal mammals is drastically im- ily.11,12) That is, the presence of prestin is essential for the OHC proved by about 40 dB by a cochlear amplifier, which is in- electromotility and for cochlear amplification. Therefore, this volved with mechano-electrical transduction (MET) located paper deals with the recent studies identifying the relationship within the stereocilia on the apex of the cells modulating re- between prestin and electromotility, the recent findings of the ceptor potentials in response to hair cell bundle deflection,1-7) structure and function of prestin, and the recent prestin-related and electromotility placed in the outer hair cell (OHC) lateral topics. wall triggering changes in the OHC length in response to the 4,8-10) receptor potentials. While MET has been observed in both OHC Electromotility and inner and outer hair cells of non-mammals and mammals, elec- Cochlear Amplification tromotility has been only observed in OHC of mammals. Re- cently, it has reported that OHC electromotility requires a volt- When acoustic signals reach the ear, they evoke the motion Copyright © 2011 The Korean Audiological Society 101 Prestin and OHC Motility electromotility is an only characteristic displayed exclusively Acoustic Basilar membrane signal motion by mammalian OHCs. The basic mechanisms of the OHC electomotility have been sought in terms of the OHC forces Hair bundle deflection and the OHC stiffness because the axial stiffness of the OHC is itself voltage dependent.18) Lateral membrane motility The OHC electromotility originates within the lateral wall Transduction 19,20) channel gating of the OHC. The anatomic structure of the OHC is essential for the motility. The OHCs are very sensitive to the osmotic Sensory signal Receptor potential strength of the external solution because the OHCs swell in re- transmission modulation Efferent input sponse to the hypo-osmotic solution while they shrink in re- sponse to the hyper-osmotic solution.21-24) Because of the cy- Fig. 1. Important steps of the positive feedback loop including the lindrical structure, swelling leads to the OHC contraction while basilar membrane motion, the hair cell bundle deflection, the effer- ent feedback from the brain, the receptor potential, and the OHC volume shrinking leads to the cell elongation. Therefore, the motility in response to the acoustic signals. OHC: outer hair cell. change of osmolality produces changes in turgor pressure of the OHC. of the basilar membrane containing a single row of inner hair The structure of the OHCs in vertebrate cells is very unique cells and three rows of OHC, which deflects the hair cell bun- because of a hydrostat with a pressured fluid core and a me- dle located in the stereocilia by opening of the transduction chanically reinforced lateral wall maintaining their cylindri- channels.13-15) When the hair cell bundle deflects to the tallest cal shape. The OHCs have the lateral wall with three sublami- stereocilia, the transduction channels open and allow K+ and nate layers containing a plasma membrane, a cytoskeleton, Ca2+ ions into the OHC, which leads to an increase of the hair and a membrane organelle called subsurface cisternae. Fig. 2 cell receptor potential resulting in depolarization.16) When the shows the lateral wall with three sublaminate layers. The hair cell bundle deflects to the opposite direction, the channels plasma membrane is a phospholipid bilayer holding many close and outflow the ions out of the OHC, which leads to a particles between the inner and outer leaflets which is re- decrease of the hair cell receptor potential resulting in hyper- cently known as prestin.18,25) The cytoskeleton contains paral- polarization. The hair cell receptor potential drives to change lel actin filaments crosslinked with spectrin, associated with the length of the OHC soma.4) Depolarization causes the OHC protein 4.1 and pillars of unknown composition tethering the to contract along its longitudinal axis while hyperpolarization actin filaments to the plasma membrane.26,27) The subsurface causes it to expand. The modulation of the length of OHC cisternae is an intracellular organelle, similar to endoplasmic leads to the change of the basilar membrane vibration. In sum- reticulum or Golgi apparatus, that lines the inside of the cyto- mary, the increased OHC receptor shortens the OHC (thick) skeleton.27,28) and moves up the basilar membrane (BM) while the decreased The OHC motility depends on particles of the lateral plasma OHC receptor elongates (thin) the cell and moves down the membrane due to an area motor in the lateral plasma mem- BM.4) This motility of the OHC is unique to only mammals. brane, a structure in the plane of the lateral membrane that can Therefore, in mammals, the OHC motility is necessary for be switched between the contraction and elongation states by cochlear amplification. Fig. 1 show the feedback loop which a change of membrane polarization.29) The particles of the is involved with cochlear amplification in terms of the mech- lateral plasma membrane are 8-10 mm in diameter with high ano-electrical transduction, electromotility, and efferent feed- densities ranging from about 3,000 µm-2 to 8,000 µm-2, which back from the brain.17) representing several different membrane proteins.30) Further- more, the OHC motility results from an actuator because the Motility and Unique Structure of OHC OHC switches between the contraction and elongation states when there is external source of energy.31) The fact that there The change of OHC length in response to electrical stimu- is no internal source of energy bought a new concept of piezo- lation was first observed by Brownell, et al.8) who reported electricity in modeling OHCs, which produces electrical forc- that depolarization by current leads to the OHC contraction es needed for electromotility at high frequencies.32) and hyperpolarization by current leads to the OHC elonga- tion. The change of the OHC length produced by electrical Pharmacology of OHC Motility stimulation has been termed electromotility. No other cell type in the mammalian cochlea displays electromotility. Therefore, There are many agents which can modulate and affect the 102 Korean J Audiol 2011;15:101-106 Choi CH Extracisternal space SSC Particles in plasma PM membrane C22 C12 Extracisternal Passive space C11 Stereocilia Electromotite response Subsurface Active a cisterna (SSC) ε θ Pillar a ε x Actin Spectrin Nucleus Fig. 2. Structure of OHC lateral wall with three sublaminate layers of a plasma membrane, a cytoskeleton, and a subsurface cisternae. Furthermore, this diagram shows the passive and active components of the OHC motility. The passive components include longitudinal (C11), circumferential (C22), and mixed (C12) elastic moduli of the orthotropic OHC wall while the active components include longitudinal a a and circumferential strain (εx and εθ ).