Phosphate analogs block adaptation in hair cells by inhibiting adaptation-motor force production

Neuron. 1996 Sep;17(3):523-33. doi: 10.1016/s0896-6273(00)80184-1.

Abstract

To ensure optimal sensitivity for mechanoelectrical transduction, hair cells adapt to prolonged stimuli using active motors. Adaptation motors are thought to employ myosin molecules as their force-producing components. We find that beryllium fluoride, vanadate, and sulfate, phosphate analogs that inhibit the ATPase activity of myosin, inhibit adaptation by abolishing motor force production. Phosphate analogs interact with a 120-kDa bundle protein, most likely myosin 1 beta, in a manner that coincides with their effects on adaptation. Features of transduction following inhibition of motor force production suggest that the gating and extent springs of the hair cell orient in parallel at rest and that the negative limit of adaptation arises when force in the stretched extent spring matches the force output of the adaptation motor.

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*
  • Beryllium / pharmacology
  • Electrophysiology
  • Fluorides / pharmacology
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / enzymology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Microdialysis
  • Models, Biological
  • Myosins / antagonists & inhibitors
  • Myosins / chemistry
  • Phosphates / physiology*
  • Photochemistry
  • Signal Transduction / physiology
  • Sulfates / pharmacology
  • Vanadates / pharmacology

Substances

  • Isoenzymes
  • Phosphates
  • Sulfates
  • Vanadates
  • beryllium fluoride
  • Myosins
  • Beryllium
  • Fluorides