The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells

Biophys J. 2008 Apr 1;94(7):2639-53. doi: 10.1529/biophysj.107.123257. Epub 2008 Jan 4.

Abstract

Sound stimuli excite cochlear hair cells by vibration of each hair bundle, which opens mechanotransducer (MT) channels. We have measured hair-bundle mechanics in isolated rat cochleas by stimulation with flexible glass fibers and simultaneous recording of the MT current. Both inner and outer hair-cell bundles exhibited force-displacement relationships with a nonlinearity that reflects a time-dependent reduction in stiffness. The nonlinearity was abolished, and hair-bundle stiffness increased, by maneuvers that diminished calcium influx through the MT channels: lowering extracellular calcium, blocking the MT current with dihydrostreptomycin, or depolarizing to positive potentials. To simulate the effects of Ca(2+), we constructed a finite-element model of the outer hair cell bundle that incorporates the gating-spring hypothesis for MT channel activation. Four calcium ions were assumed to bind to the MT channel, making it harder to open, and, in addition, Ca(2+) was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca(2+) effects on adaptation and bundle mechanics comparable to those measured experimentally. We suggest that fast adaptation and force generation by the hair bundle may stem from the action of Ca(2+) on the channel complex and do not necessarily require the direct involvement of a myosin motor. The significance of these results for cochlear transduction and amplification are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Animals, Newborn
  • Calcium / pharmacology*
  • Cells, Cultured
  • Cochlea / drug effects
  • Cochlea / physiology
  • Computer Simulation
  • Elasticity
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / physiology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Mechanotransduction, Cellular / physiology*
  • Models, Biological*
  • Motion
  • Movement / drug effects
  • Movement / physiology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Calcium