CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING |
The actions of calcium on hair bundle mechanics in mammalian cochlear hair cells
Maryline Beurg 1, Jong-Hoon Nam 2, Andrew Crawford 3 and Robert Fettiplace 2*
1 INSERM, Université Victor Segalen Bordeaux 2, Hôpital Pellegrin, 33076 Bordeaux, France
2 University of Wisconsin Madison
3 University of Cambridge, UK
* To whom correspondence should be addressed. E-mail: fettiplace{at}physiology.wisc.edu.
Submitted on October 4, 2007
Revised on November 6, 2007
Accepted on 4 December 2007
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Abstract |
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Sound stimuli excite cochlear hair cells by vibration of each hair bundle that opens mechanotransducer (MT) channels. We have measured hair bundle mechanics in isolated rat cochleas by stimulating with flexible glass fibers during simultaneous recording of the MT current. Both inner and outer hair cell bundles possessed force displacement relationships exhibiting a non-linearity reflecting a time-dependent reduction in stiffness. The non-linearity 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 incorporating 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 the results for cochlear transduction and amplification are discussed.
Key Words:
adaptation, calcium, finite element, hair bundle, hair cell, stiffness
