title: The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells.
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.
authors.affiliation: INSERM U587, Université Victor Segalen Bordeaux, Hôpital Pellegrin, Bordeaux, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Beurg
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Nam
authors.forename: Andrew
authors.initials: A
authors.lastname: Crawford
authors.forename: Robert
authors.initials: R
authors.lastname: Fettiplace
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D004548:Elasticity; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D009038:Motion; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002118:Calcium