Skip to main content
Log in

Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse

  • Published:
Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

The development of motor protein activity in the lateral membrane of the mouse outer hair cell (OHC) from postnatal day 5 (P5) to P18 was investigated under whole-cell voltage clamp. Voltage-dependent, nonlinear capacitance (C v), which represents the conformational fluctuations of the motor molecule, progressively increased during development. At P12, the onset of hearing in the mouse, C v was about 70% of the mature level. C v saturated at P18 when hearing shows full maturation. On the other hand, C lin, which represents the membrane area of the OHC, showed a relatively small increase with development, reaching steady state at P10. This early maturation of linear capacitance is further supported by morphological estimates of surface area during development. These results, in light of recent prestin knockout experiments and our results with quantitative polymerase chain reaction, suggest that, rather than the incorporation of new motors into the lateral membrane after P10, molecular motors mature to augment nonlinear capacitance. Thus, current estimates of motor protein density based on charge movement may be exaggerated. A corresponding indicator of motor maturation, the motor’s operating voltage midpoint, V pkcm, tended to shift to depolarized potentials during postnatal development, although it was unstable prior to P10. However, after P14, V pkcm reached a steady-state level near −67 mV, suggesting that intrinsic membrane tension or intracellular chloride, each of which can modulate V pkcm, may mature at P14. These developmental data significantly alter our understanding of the cellular mechanisms that control cochlear amplification and provide a foundation for future analysis of genetic modifications of mouse auditory development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ashmore JF (1987) A fast motile response in guinea-pig outer hair cells: The cellular basis of the cochlear amplifier. J Physiol 388:323–347

    PubMed  CAS  Google Scholar 

  • Ashmore JF (1990) Forward and reverse transduction in the mammalian cochlea. Neurosci Res Suppl 12:S39–S50

    Article  PubMed  CAS  Google Scholar 

  • Belyantseva IA, Adler HJ, Curi R, Frolenkov GI, Kachar B (2000) Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells. J Neurosci 20:RC116

    PubMed  CAS  Google Scholar 

  • Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y (1985) Evoked mechanical responses of isolated cochlear outer hair cells. Science 227:194–196

    Article  PubMed  CAS  Google Scholar 

  • Dallos P (1992) The active cochlea. J Neurosci 12:4575–4585

    PubMed  CAS  Google Scholar 

  • Dallos P, Evans BN (1995) High-frequency motility of outer hair cells and the cochlear amplifier. Science 267:2006–2009

    Article  PubMed  CAS  Google Scholar 

  • Dallos P, Santos-Sacchi J, Flock A (1982) Intracellular recordings from cochlear outer hair cells. Science 218:582–584

    Article  PubMed  CAS  Google Scholar 

  • Deak L, Zheng J, Orem A, Du GG, Aguinaga S, Matsuda K, Dallos P (2005) Effects of cyclic nucleoticles on the function of prestin. J Physiol 563:483–496

    Article  PubMed  CAS  Google Scholar 

  • Ehret G (1976) Development of absolute auditory thresholds in the house mouse (Mus musculus). J Am Audiol Soc 1:179–184

    PubMed  CAS  Google Scholar 

  • Forge A, Souter M, Denman Johnson K (1997) Structural development of sensory cells in the ear. Semin Cell Dev Biol 8:225–237

    Article  PubMed  Google Scholar 

  • Frank G, Hemmert W, Gummer AW (1999) Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. Proc Natl Acad Sci USA 96:4420–4425

    Article  PubMed  CAS  Google Scholar 

  • Frolenkov GI, Mammano F, Belyantseva IA, Coling D, Kachar B (2000) Two distinct Ca2+-dependent signaling pathways regulate the motor output of cochlear outer hair cells. J Neurosci 20:5940–5948

    PubMed  CAS  Google Scholar 

  • Gale JE, Ashmore JF (1994) Charge displacement induced by rapid stretch in the basolateral membrane of the guinea-pig outer hair cell. Proc R Soc Lond B Biol Sci 255:243–249

    Article  CAS  Google Scholar 

  • Geleoc GS, Casalotti SO, Forge A, Ashmore JF (1999) A sugar transporter as a candidate for the outer hair cell motor. Nat Neurosci 2:713–719

    Article  PubMed  CAS  Google Scholar 

  • He DZ, Evans BN, Dallos P (1994) First appearance and development of electromotility in neonatal gerbil outer hair cells. Hear Res 78:77–90

    Article  PubMed  CAS  Google Scholar 

  • Huang G, Santos-Sacchi J (1993a) Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation. Biophys J 65:2228–2236

    CAS  Google Scholar 

  • Huang G-J, Santos-Sacchi J (1993b) Metabolic control of OHC function: Phosphorylation and dephosphorylation agents shift the voltage dependence of motility related capacitance. Assoc Res Otolaryngol Abs 16:464

    Google Scholar 

  • Iwasa KH (1993) Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophys J 65:492–498

    PubMed  CAS  Google Scholar 

  • Iwasa KH (1994) A membrane motor model for the fast motility of the outer hair cell. J Acoust Soc Am 96:2216–2224

    Article  PubMed  CAS  Google Scholar 

  • Kakehata S, Santos-Sacchi J (1995) Membrane tension directly shifts voltage dependence of outer hair cell motility and associated gating charge. Biophys J 68:2190–2197

    PubMed  CAS  Google Scholar 

  • Kalinec F, Holley MC, Iwasa KH, Lim DJ, Kachar B (1992) A membrane-based force generation mechanism in auditory sensory cells. Proc Natl Acad Sci USA 89:8671–8675

    Article  PubMed  CAS  Google Scholar 

  • Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J (2002) Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 419:300–304

    Article  PubMed  CAS  Google Scholar 

  • Ludwig J, Oliver D, Frank G, Klocker N, Gummer AW, Fakler B (2001) Reciprocal electromechanical properties of rat prestin: The motor molecule from rat outer hair cells. Proc Natl Acad Sci USA 98:4178–4183

    Article  PubMed  CAS  Google Scholar 

  • Marcotti W, Kros CJ (1999) Developmental expression of the potassium current Ik, n contributes to maturation of mouse outer hair cells. J Physiol 520:653–660

    Article  Google Scholar 

  • Oliver D, Fakler B (1999) Expression density and functional characteristics of the outer hair cell motor protein are regulated during postnatal development in rat. J Physiol 519(pt 3):791–800

    Article  PubMed  CAS  Google Scholar 

  • Oliver D, He DZ, Klocker N, Ludwig J, Schulte U, Waldegger S, Ruppersberg JP, Dallos P, Fakler B (2001) Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science 292:2340–2343

    Article  PubMed  CAS  Google Scholar 

  • Pujol R, Zajic G, Dulon D, Raphael Y, Altschuler RA, Schacht J (1991) First appearance and development of motile properties in outer hair cells isolated from guinea-pig cochlea. Hear Res 57:129–141

    Article  PubMed  CAS  Google Scholar 

  • Reisinger E, Zimmermann U, Knipper M, Ludwig J, Klocker N, Fakler B, Oliver D (2005) Cod106, a novel synaptic protein expressed in sensory hair cells of the inner ear and in CNS neurons. Mol Cell Neurosci 28:106–117

    Article  PubMed  CAS  Google Scholar 

  • Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K (1999) The K+/Cl co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397:251–255

    Article  PubMed  CAS  Google Scholar 

  • Rybalchenko V, Santos-Sacchi J (2003) Cl flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig. J Physiol 547:873–891

    Article  PubMed  CAS  Google Scholar 

  • Santos-Sacchi J (1990) Fast outer hair cell motility: How fast is fast? In: Dallos P, Geisler CD, Matthews JW, Ruggero MA, Steele CR, editors. The Mechanics and Biophysics of Hearing. Springer-Verlag, Berlin, pp. 69–75

    Google Scholar 

  • Santos-Sacchi J (1991) Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J Neurosci 11:3096–3110

    PubMed  CAS  Google Scholar 

  • Santos-Sacchi J (1992) On the frequency limit and phase of outer hair cell motility: Effects of the membrane filter. J Neurosci 12:1906–1916

    PubMed  CAS  Google Scholar 

  • Santos-Sacchi J (1993) Harmonics of outer hair cell motility. Biophys J 65:2217–2227

    PubMed  CAS  Google Scholar 

  • Santos-Sacchi J (2004) Determination of cell capacitance using the exact empirical solution of dY/dCm and its phase angle. Biophys J 87:714–727

    Article  PubMed  CAS  Google Scholar 

  • Santos-Sacchi J, Dilger JP (1988) Whole cell currents and mechanical responses of isolated outer hair cells. Hear Res 35:143–150

    Article  PubMed  CAS  Google Scholar 

  • Santos-Sacchi J, Kakehata S, Takahashi S (1998) Effects of membrane potential on the voltage dependence of motility-related charge in outer hair cells of the guinea-pig. J Physiol 510(pt 1):225–235

    Article  PubMed  CAS  Google Scholar 

  • Santos-Sacchi J, Navarrete E (2002) Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor. Pfluegers Arch 444:99–106

    Article  CAS  Google Scholar 

  • Santos-Sacchi J, Shen WX, Zheng J, Dallos P (2001) Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein. J Physiol 531:661–666

    Article  PubMed  CAS  Google Scholar 

  • Shnerson A, Devigne C, Pujol R (1981) Age-related changes in the C57BL/6J mouse cochlea. II. Ultrastructural findings. Brain Res 254:77–88

    PubMed  CAS  Google Scholar 

  • Shnerson A, Pujol R (1981) Age-related changes in the C57BL/6J mouse cochlea. I. Physiological findings. Brain Res 254:65–75

    PubMed  CAS  Google Scholar 

  • Solsona C, Innocenti B, Fernandez JM (1998) Regulation of exocytotic fusion by cell inflation. Biophys J 74:1061–1073

    Article  PubMed  CAS  Google Scholar 

  • Song L, McGee J, Walsh EJ (2006) Frequency- and level-dependent changes in auditory brainstem responses (ABRs) in developing mice. J Acoust Soc Am 119:2242–2257

    Article  PubMed  Google Scholar 

  • Song L, Seeger A, Santos-Sacchi J (2005) On membrane motor activity and chloride flux in the outer hair cell: Lessons learned from the environmental toxin tributyltin. Biophys J 88:2350–2362

    Article  PubMed  CAS  Google Scholar 

  • Souter M, Forge A (1998) Intercellular junctional maturation in the stria vascularis: Possible association with onset and rise of endocochlear potential. Hear Res 119:81–95

    Article  PubMed  CAS  Google Scholar 

  • Souter M, Nevill G, Forge A (1995) Postnatal development of membrane specialisations of gerbil outer hair cells. Hear Res 91:43–62

    Article  PubMed  CAS  Google Scholar 

  • Steel KP, Bock GR (1980) The nature of inherited deafness in deafness mice. Nature 288:159–161

    Article  PubMed  CAS  Google Scholar 

  • Weber T, Zimmermann U, Winter H, Mack A, Kopschall I, Rohbock K, Zenner HP, Knipper M (2002) Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin. Proc Natl Acad Sci USA 99:2901–2906

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Gao J, Guo Y, Zuo J (2004) Hearing threshold elevation precedes hair-cell loss in prestin knockout mice. Brain Res Mol Brain Res 126:30–37

    Article  PubMed  CAS  Google Scholar 

  • Zheng J, Shen W, He D, Long K, Madison L, Dallos P (2000a) Prestin is the motor protein of cochlear outer hair cells. Nature 405:149–155

    Article  CAS  Google Scholar 

  • Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P (2000b) Prestin is the motor protein of cochlear outer hair cells. Nature 405:149–155

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to S. K., H. S.), NIH grants DC00273 (to J. S.-S.) and K08 DC05352 (to D. N.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seiji Kakehata.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe, T., Kakehata, S., Kitani, R. et al. Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse. J Membrane Biol 215, 49–56 (2007). https://doi.org/10.1007/s00232-007-9004-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-007-9004-5

Keywords

Navigation