Fate of mammalian cochlear hair cells and stereocilia after loss of the stereocilia

J Neurosci. 2009 Dec 2;29(48):15277-85. doi: 10.1523/JNEUROSCI.3231-09.2009.

Abstract

Cochlear hair cells transduce mechanical stimuli into electrical activity. The site of hair cell transduction is the hair bundle, an array of stereocilia with different height arranged in a staircase. Tip links connect the apex of each stereocilium to the side of its taller neighbor. The hair bundle and tip links of hair cells are susceptible to acoustic trauma and ototoxic drugs. It has been shown that hair cells in lower vertebrates and in the mammalian vestibular system may survive bundle loss and undergo self-repair of the stereocilia. Our goals were to determine whether cochlear hair cells could survive the trauma and whether the tip link and/or the hair bundle could be regenerated. We simulated the acoustic trauma-induced tip link damage or stereociliary loss by disrupting tip links or ablating the hair bundles in the cultured organ of Corti from neonatal gerbils. Hair-cell fate and stereociliary morphology and function were examined using confocal and scanning electron microscopies and electrophysiology. Most bundleless hair cells survived and developed for approximately 2 weeks. However, no spontaneous hair-bundle regeneration was observed. When tip links were ruptured, repair of tip links and restoration of mechanotransduction were observed in <24 h. Our study suggests that the dynamic nature of the hair cell's transduction apparatus is retained despite the fact that regeneration of the hair bundle is lost in mammalian cochlear hair cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Biomechanical Phenomena
  • Chelating Agents / pharmacology
  • Cilia / drug effects
  • Cilia / physiology
  • Cilia / ultrastructure
  • Cochlea / cytology*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Gerbillinae
  • Hair Cells, Auditory / cytology*
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / physiology*
  • Hair Cells, Auditory / ultrastructure
  • Mechanotransduction, Cellular / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Microscopy, Confocal / methods
  • Microscopy, Electron, Scanning / methods
  • Organ Culture Techniques
  • Patch-Clamp Techniques / methods
  • Physical Stimulation

Substances

  • Chelating Agents
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid