Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation

Neuron. 2004 Oct 14;44(2):309-20. doi: 10.1016/j.neuron.2004.09.020.


After opening in response to mechanical stimuli, hair cell transduction channels adapt with fast and slow mechanisms that each depend on Ca(2+). We demonstrate here that transduction and adaptation require phosphatidylinositol 4,5-bisphosphate (PIP(2)) for normal kinetics. PIP(2) has a striking distribution in hair cells, being excluded from the basal region of hair bundles and apical surfaces of frog saccular hair cells. Localization of a phosphatidylinositol lipid phosphatase, Ptprq, to these PIP(2)-free domains suggests that Ptprq maintains low PIP(2) levels there. Depletion of PIP(2) by inhibition of phosphatidylinositol 4-kinase or sequestration by aminoglycosides reduces the rates of fast and slow adaptation. PIP(2) and other anionic phospholipids bind directly to the IQ domains of myosin-1c, the motor that mediates slow adaptation, permitting a strong interaction with membranes and likely regulating the motor's activity. PIP(2) depletion also causes a loss in transduction current. PIP(2) therefore plays an essential role in hair cell adaptation and transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adaptation, Physiological / physiology*
  • Animals
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Hair Cells, Auditory, Inner / drug effects
  • Hair Cells, Auditory, Inner / physiology*
  • Hair Cells, Auditory, Inner / ultrastructure
  • Immunohistochemistry
  • Mechanotransduction, Cellular / drug effects
  • Mechanotransduction, Cellular / physiology*
  • Microscopy, Electron
  • Myosins / metabolism
  • Patch-Clamp Techniques
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Protein Tyrosine Phosphatases / drug effects
  • Protein Tyrosine Phosphatases / metabolism
  • Rana pipiens


  • Enzyme Inhibitors
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Tyrosine Phosphatases
  • Myosins