February 13, 2008 | David F. Coppedge

Fast Protein Fine-Tunes the Ear

Remember prestin?  It’s a motor protein in the inner ear, discovered in 2001 (03/27/2001), that acts so fast – within millionths of a second – its discoverers named it after the word “presto!” (02/21/2002).  Scientists have been studying its role as a volume adjuster (07/31/2007) that allows it to amplify sound 10,000-fold (09/19/2002) .  New evidence suggests that prestin also fine-tunes the pitch across the audible range.  A paper on this appeared this week in Current Biology.1
    The human ear responds to volume differences over 12 orders of magnitude – a phenomenal dynamic range, allowing us to hear the faintest whisper of a breeze to the roar of a jet engine.  If the cochlea had the same sensitivity throughout the dynamic range, the result would be literally deafening.  The cochlea has, therefore, both fast-adaptation and slow-adaptation mechanisms to quench overpowering sounds.  An analogy might be to a sound system that instantly cuts off ear-piercing feedback then adjusts the volume level by a slider.  Prestin has been implicated in fast-adaptation.  It stiffens the outer hair cells to prevent loud sounds from blowing them over, but loosens them to respond to gentle vibrations.
    The authors began their abstract, “The remarkable power amplifier of the cochlea boosts low-level and compresses high-level vibrations of the basilar membrane.”  This means your ears have a high-tech device, familiar to audio technicians, called a compressor-limiter.  You’re not hearing what is really “out there” in its raw form.  Your ear is protecting your brain by delivering processed sound.  It automatically turns up the volume on the soft sounds, and turns it down on the loud sounds.
    The authors of this paper agreed that prestin is the prime contender for the power amplifier, but then found something even more amazing: prestin tunes the pitch, too.  They found to their surprise that mice with prestin knocked out were just as sensitive in the high-frequency range – but heard sounds a half-octave too low.  There appears to be a trade-off between volume sensitivity and pitch accuracy that prestin, somehow, solves.  To do this, the motor protein must be able to parse the frequency spectrum of the sound wave.  Here it is in their technical jargon:

We propose that the absence of prestin from OHCs [outer hair cells in the cochlea], and consequent reduction in stiffness of the cochlea partition, changes the passive impedance of the BM [basilar membrane] at high frequencies, including the CF [characteristic frequency].  We conclude that prestin influences the cochlear partition’s dynamic properties that permit transmission of its vibrations into neural excitation.  Prestin is crucial for defining sharp and sensitive cochlear frequency tuning by reducing the sensitivity of the low-frequency tail of the tuning curve, although this necessitates a cochlear amplifier to determine the narrowly tuned tip.


1.  Lagarde, Drexl, Lukashkin, Zuo and Russell, “Prestin’s Role in Cochlear Frequency Tuning and Transmission of Mechanical Responses to Neural Excitation,”

Whatever is going on inside your head, when it works, it works extremely well.  The mechanisms at work to provide such exquisite sensitivity to the tiniest of air vibrations are still being figured out.  This paper shows that the initial models of how prestin works are too simple.  Their experiments on mice with and without prestin “provides further indication that neural tuning is not a direct consequence of BM [basilar membrane] tuning but depends on complex interaction between the various elements of the cochlear partition,” including prestin and the arrangement of the hair cell bundles.
    Everything works as a functional unit.  Did you hear anything about evolution?  We hope not, because they never used the E-word once in their entire paper.  Their language was the lingo of auditory engineering: microphones, characteristic frequencies, amplifiers, compressor-limiters, thresholds, dynamic range and frequency response.  Ask a sound technician if he operates by random mutation and natural selection.  You are likely to get an earful.

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