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Originally published as Biophys J. BioFAST on January 4, 2008.
doi:10.1529/biophysj.107.123257
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Biophysical Journal 94:2639-2653 (2008)
© 2008 The Biophysical Society

The Actions of Calcium on Hair Bundle Mechanics in Mammalian Cochlear Hair Cells

Maryline Beurg *, Jong-Hoon Nam {dagger}, Andrew Crawford {ddagger} and Robert Fettiplace {dagger}

* INSERM U587, Université Victor Segalen Bordeaux, Hôpital Pellegrin, Bordeaux, France; {dagger} Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin; and {ddagger} Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, United Kingdom

Correspondence: Address reprint requests to Robert Fettiplace, 185 Medical Scices Bldg., 1300 University Ave., Madison, WI 53706. Tel.: 608-262-9320; Fax: 608-265-3500; E-mail: fettiplace{at}physiology.wisc.edu.

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 Ca2+, 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, Ca2+ was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca2+ 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 Ca2+ 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.




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