Biochemistry of

Hearing
 The auditory sense organ.

Martin Schwander et al. J Cell Biol 2010;190:9-20

© 2010 Schwander et al.

Remarkable Properties of the Auditory
System
• inner ear:
- responds to sound-induced vibrations of less
than a nanometer
- can amplify signals by more than 100-fold
- has a wide dynamic range enabling humans to
perceive frequencies from 20 Hz to 20 kHz
Remarkable Properties of the Auditory
System
• essential for the extraordinary capability:
- mechanosensory hair cells
- supporting cells
- accessory extracellular structures

• organ of Corti:
- within the snail-shaped cochlea of the inner ear
- formed by the above cells/structures
 Human Organ of Corti

• harbors 16,000 hair cells patterned in:

- one row of inner hair cells (IHCs)
- three rows of outer hair cells (OHCs
 Hair Cells of Human Organ of Corti
• hair bundle:
- located at the apical surface
- it’s the mechanically sensitive organelle consists:
l dozens of stereocilia
• tectorial membrane:
- the extracellular matrix
- covers the apical surface of the organ of Corti
- attached to the stereociliary bundles of OHCs
 Hair Cells of Human Organ of Corti
• cell bodies of hair cells:
- form tight connections with support cells:
l adhere at their basal surface to an additional
extracellular matrix:
- basilar membrane
 The auditory sense organ.

Martin Schwander et al. J Cell Biol 2010;190:9-20

© 2010 Schwander et al.

 Initiation of Hearing

• oscillations in air pressure are converted into

fluid pressure that travel down the cochlear
duct
• induce vibrations in the basilar membrane
• vibrations are then transferred onto hair cells
• leads to detection by the hair bundles
• the opening of mechanically gated ion
channels
• hair cell depolarization
 Initiation of Hearing

• hair cells at the base of the duct respond to

highest frequencies
• hair cells at the apex respond to the lowest
frequencies

• because of gradual changes in the features

of the organ of Corti:
- the height of stereocilia
- width & thickness of the basilar membrane
• cochlear amplifier:
- depends on OHCs
- active feedback mechanisms amplifying basilar
membrane motion because viscous damping in
the cochlea would otherwise dissipate sound
energy
- has a remarkable compressive nonlinearity
l this ensures that soft sounds are amplified more
strongly than loud sounds
• when passive basilar membrane resonance
is induced by a pure tone at its
corresponding frequency position along the
cochlear duct:
- OHCs are locally activated
- enhance basilar membrane vibration

• IHCs detect these vibrations and activate

afferent neurons
 The auditory sense organ.

Martin Schwander et al. J Cell Biol 2010;190:9-20

© 2010 Schwander et al.
 Hair bundle development and structure.

Martin Schwander et al. J Cell Biol 2010;190:9-20

© 2010 Schwander et al.
 Hair bundle proteins.

Martin Schwander et al. J Cell Biol 2010;190:9-20

© 2010 Schwander et al.
 Hair bundles and mechanotransduction.

© 2010 Schwander et al. Martin Schwander et al. J Cell Biol 2010;190:9-20

 Hair Cells and the
Mechanoelectrical
Transduction of Sound
Waves
 Hair Cell
• is an evolutionary triumph
• solves the problem of transforming vibrational
energy into an electrical signal
• scale at which the hair cell operates is truly
amazing:
- at the limits of human hearing:
l can faithfully detect movements of atomic dimensions
l respond in the tens of microseconds
• can adapt rapidly to constant stimuli:
- allows the listener to extract signals from a noisy
background
 Hair Cell

• is a flask-shaped epithelial cell

• named for the bundle of hairlike processes that
protrude from its apical end into the scala media:
- each hair bundle contains:
l 30 to a few hundred hexagonally arranged stereocilia
l one taller kinocilium
• Kinocilium:
- it’s the only one with a true ciliary structure
- with the characteristic two central tubules surrounded by
nine doublet tubules (Figure B)
- function is unclear
- it actually disappears shortly after birth in the cochlea of
humans and other mammals (Figure C)
Stereocilia:
- are simpler, containing only an actin
cytoskeleton
- each stereocilium tapers where it
inserts into the apical membrane:
l forms a hinge about which each
stereocilium pivots (Figure 13.7D
- are graded in height
- are arranged in a bilaterally
symmetric fashion:
l in vestibular hair cells, hair cells, this
plane runs through the kinocilium
Stereocilia:
• displacement of the hair bundle
parallel to this plane toward the tallest
stereocilia:
- depolarizes the hair cell
• movements parallel to this plane
toward the shortest stereocilia:
- cause hyperpolarization
• in contrast, displacements
perpendicular to the plane of
symmetry do not alter the hair cell's
membrane potential
• hair bundle movements at the
threshold of hearing are
approximately 0.3 nm
 Hair Cell
• convert the displacement of the stereociliary bundle
into an electrical potential in as little as 10
microseconds:
- such speed is required to:
l faithfully transduce high-frequency signals
l enable the accurate localization of the source of the sound

• a direct, mechanically gated transduction channel:

- meets the need for microsecond resolution
- ruling out the relatively slow second messenger pathways
used in visual and olfactory transduction
 Hair Cell
Tip links:
• filamentous structures that
connect the tips of adjacent
stereocilia
• directly open cation-selective
transduction channels when
stretched:
- allows K+ ions to flow into the cell
(see Figure 13.7D)
 Hair Cell
• Pivoting of linked stereocilia from side to side:
- varies the tension on the tip link :
l modulating the ionic flow:
- resulting in a graded receptor potential that follows the movements
of the stereocilia (Figure 13.8)

• tip link model:

- a fine filament connects the tip of each stereocilium along
the axis to the side of its taller neighbor
l only deflections along the axis of the hair bundle activate
transduction channels
 Proteins of Tip Link
• cadherin 23:
- a long cadherin with 27 extracellular domains
- related to hereditary deafness
- present in stereocilia
- may be part of the tip links or transient lateral links of hair
cells
http://www.bmb.leeds.ac.uk/illingworth
/bioc3800/#15602018
Box B
Adaptation & Tuning of Vestibular Hair Cells
• Hair Cell Adaptation
• at sensory threshold:
- minuscule movement of the hair bundle has been
compared to the displacement of the top of the Eiffel
Tower by a thumb's breadth
- can still adapt quickly and continuously to static
displacements of the hair bundle caused by large
movements
Box B
Adaptation & Tuning of Vestibular Hair Cells
• Hair Cell Adaptation
• great sensitivity:
- hair cell can still adapt quickly & continuously to static
displacements of the hair bundle caused by large
movements:
l especially useful in the otolith organs:
l where adaptation permits hair cells to maintain sensitivity to small
linear and angular accelerations of the head despite the
constant input from gravitational forces that are over a million
times greater
Box B Adaptation
• receptor potential generation:
- occurs in both directions when the hair bundle is
displaced:
l at different rates for each direction

• when hair bundle is pushed toward the kinocilium:

- tension is initially increased in the gating spring
- during adaptation:
l tension decreases back to the resting level

• when the hair bundle is displaced away from the

kinociliumin:
- tension in the spring initially decreases
- during adaptation:
l then involves an increase in spring tension
Box B Adaptation

• One theory:
- a Ca2+ regulated motor such as a myosin ATPase climbs
along actin filaments in the stereocilium:
l actively resets the tension in the transduction spring
Box B Adaptation
• during sustained depolarization:
- Ca2+ enters through the transduction channel, along with K+
- Ca2+ then causes the motor to spend a greater fraction of its
time unbound from the actin:
l resulting in slippage of the spring down the side of the stereocilium

• during sustained hyperpolarization:

- Ca2+ levels drop below normal resting levels
- the motor spends more of its time bound to the actin:
l thus climbing up the actin filaments and increasing the spring
tension
Box B Adaptation
• As tension increases:
- some of the previously closed transduction channels
open:
l admitting Ca2+:
- thus slowing the motor's progress until a balance is struck
between the climbing and slipping of the motor

• Support of this model (of hair cell adaptation):

- when internal Ca2+ is reduced artificially:
l spring tension increases
- presents an elegant molecular solution to the regulation
of a mechanical process
Box B
• Electrical Tuning
• other tuning mechanisms are especially important in
the otolith organs, where, unlike the cochlea:
- there are no obvious macromechanical resonances to
selectively filter and/or enhance biologically relevant
movements

• one such mechanism is an electrical resonance

displayed by hair cells in response to depolarization:
- membrane potential of a hair cell undergoes damped
sinusoidal oscillations at a specific frequency in response
to the injection of depolarizing current pulses (figure B).
Box B
• ionic mechanism of this process involves two major
types of ion channels located in the membrane of
the hair cell soma:
- first of these is a voltage activated Ca2+ conductance:
l lets Ca2+ into the cell soma in response to depolarization, such as
that generated by the transduction current
- second is a Ca2+-activated K+ conductance:
l is triggered by the rise in internal Ca2+ concentration
l activation occurs 10 to 100 times faster than that of similar
currents in other cells
l such rapid kinetics allow this conductance to generate an
electrical response that usually requires the fast properties of
a voltage-gated channel

• these two currents produce an interplay of

depolarization and repolarization that results in
electrical resonance (figure C)
Box B
• resultant receptor potential is largest at the frequency of
electrical resonance(resonance frequency):
l represents the characteristic frequency of the hair cell
l transduction at that frequency will be most efficient
l has important implications for structures like
the utricle and sacculus:
- may encode a range of characteristic frequencies based on the
different resonance frequencies of their constituent hair cells
• electrical tuning in the otolith organs:
- can generate enhanced tuning to biologically relevant
frequencies of stimulation:
l even in the absence of macromechanical resonances within
these structures