@article{leitner_physiologie_dr.)_2012, 
  title={Molekulare Eigenschaften und pathophysiologische Relevanz der charakteristischen K+ Leitfähigkeit in cochleären äußeren Haarzellen}, 
  DOI={10.17192/z2012.0825}, 
  abstractNote={Cochlear outer hair cells (OHCs)
      are characterised by the voltage-dependent K+ conductance
      IK,n that previously was shown to be mediated by KCNQ4 (Kv7)
      channel subunits. IK,n/KCNQ4 dominates the electrical
      properties of the OHC cell membrane and furthermore is
      essential for OHC survival. Genetic deletion of KCNQ4 causes
      progressive degeneration of OHCs and deafness. Similarly,
      KCNQ4 loss-of-function mutations cause the progressive form
      of hereditary deafness DFNA2. The molecular mechanism leading
      to OHC degeneration remains elusive, but the survival of OHCs
      has been linked directly to KCNQ4 channel function.
      Strikingly, the loss of OHCs is phenotypically similar to OHC
      degeneration caused by ototoxic substances and noise damage
      (acquired hearing loss), but a role of IK,n/KCNQ4 in acquired
      hearing loss has never been investigated so far. In the
      present study I investigated the pathophysiological relevance
      of IK,n for OHC degeneration caused by aminoglycoside (AG)
      antibiotics. Since KCNQ4 channel function is essential for
      OHC survival, chemical current augmentation may provide a
      protective strategy against KCNQ4-related hearing loss. Thus,
      I analysed whether chemical KCNQ channel openers rescued IK,n
      currents from pathological inhibition. In brief, I found that
      AGs rapidly entered OHCs and that entry was necessary for
      IK,n current inhibition. The inhibition was caused by
      functional depletion of phospholipids by the AGs that are
      essential for the function of IK,n/KCNQ4. Various AGs exhibit
      different ototoxic potential, i.e. neomycin causes OHC
      degeneration whereas gentamicin damages vestibular hair
      cells. Strikingly, the degree of IK,n inhibition (neomycin
      > gentamicin) correlated with the phospholipid
      binding efficiency and with the ototoxic potential of the
      respective AG. Given the dependence of OHCs on IK,n, the
      o [...]}, 
  publisher={Philipps-Universität Marburg}, 
  author={Leitner, Michael and Physiologie and Dr.)}, 
  year={2012}, 
  month={Sep}
  }