Auditory Periphery: Cochlear Processing
Fabio Mammano
Laboratory of Biophysics, International School for Advanced Studies, Trieste, Italy
‘Mammano F. Auditory periphery: cochlear processing. Scand Audiol 1997:26 (Suppl 46):5-8,
Key words: Basilar membrane, cochlea, hair cell, hearing, sound.
Address for offprints: Fabio Mammano, SISSA, Via Beirut, 2/4, 34014 Trieste, Italy
Introduction
For over 50 years, propagation of travelling waves on the
basilar membrane of the cochlea has been known to
underlie generation of the auditory sensation (von
Békésy, 1960). Physiology textbooks so far give only a
graphical representation of this phenomenon, stressing
action potential generation on the afferent acoustic nerve
fibres contacting inner hair cells. These produce a
receptor potential upon displacement of their stereocilia
bundle: a process called forward transduction. Stereo-
cilia deflection is caused by the shearing motion of the
tectorial membrane relative to the organ of Corti, which
rides on the basilar membrane as the wave pushes it up
and down. In this type of representation the organ of
Corti has no internal degrees of freedom. Besides, the
fact that the more numerous outer hair cells are
prevalently contacted by efferent innervation (Spoendlin,
1978) is completely overlooked.
At the beginning of the 1980s crucial experiments
performed on the guinea pig basilar membrane showed
that travelling wave amplitudes are several orders of
magnitude larger in vivo than post-mortem, or even
post-trauma (Sellick et al., 1982, 1983; Johnstone et al.,
1986). The wave amplitude profiles are also rather
different in a properly functioning cochlea, being much
mote peaked and terminating abruptly after reaching
their maximum, When the wave amplitude is plotted
against stimulus frequency at a fixed site on the basilar
membrane, the slope on the falling high-frequency skirt
is hundreds of dB/octave for near-threshold acoustic
inputs. Davis (1983) called “cochlear amplifier’’ the
physiologically vulnerable process that underlies travel-
ling wave amplification. A cochlea with amplification is
said to be active, in contrast to the passive one typical
of von Békésy’s description. Here I discuss some key
results concerning the mechanisms of travelling wave
amplification in an active cochlea.
The Cochlear Amplifier
The quest for the cochlear amplifier fired a spate of
research world-wide. Outer hair cells isolated in a dish
were found to respond to extracellular sinusoidal low-
frequency electric fields with cycles of contraction!
elongation (Brownell et al., 1985). Motile responses
could be elicited at acoustic frequencies by changing the
transmembrane voltage under whole-cell patch-clamp
conditions (Ashmore, 1987). The conversion of elec-
trical stimuli into motile responses was called reverse
transduction, and the equation cochlear-amplifier cell-
motility readily established. But how exactly can cell
motility affect the propagation of travelling waves in the
cochlea?
The basic requirement for amplification is that the
forces generated by the outer hair cells be large enough
to move the basilar membrane, We tested this hypothesis
in ‘an isolated cochlea preparation, perfused with
oxygenated artificial perilymph, using a displacement-
sensitive interferometer. The outer hair cells were
stimulated with current passed across the intact cochlear
partition. We found that the organ of Corti distorted
under the action of electrically-driven cell length
changes and produced place-specific vibration of the
basilar membrane with magnitude comparable to that
observed near auditory threshold. These experiments
supplied the first direct evidence that cochlear amplifica-
tion arises from the properties of the outer hair cell
population. We also demonstrated that each transversal
section of the partition possesses at least one internal
degree of freedom, as the top of the organ of Corti, the
Scand Audiol 26, Sp 466 F Mammano
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Scand Audiol 26, Sup 46reticular lamina, and the basilar membrane moved in
antiphase when the cells were stimulated (Mammano
and Ashmore, 1993).
Inside the Motor
‘The normal pattern of motion of the basilar membrane in,
response to current passed across the cochlear partition
was a damped oscillation of up to Snm at the
characteristic frequency appropriate for the recording
site (Mammano & Ashmore, 1995). When 10mM
sodium-salicylate was added to the perfusion, the
electrically-evoked basilar-membrane motion was dras-
tically but reversibly reduced within minutes (Mammano
& Ashmore, 1993; Ashmore et al., 1995). Noticeably,
salicylates (aspirin) are known to induce hearing
threshold elevation (Douek et al., 1983), reduction of
otoacoustic emissions (McFadden & Plattsmier, 1984)
and tinnitus.
When outer hair cells in the same preparation were
patch-clamped under direct visual inspection, measur-
able changes in length could be elicited by rapidly
changing the cell potential. For typical depolarizing
commands of between 50 and 100 mV from rest, the cell
shortened by up to 1.5 ym. An appreciable displacement
of neighbouring cells was also apparent as distortions of
the cochlear partition induced by stimulating a single cell
were mechanically propagated over a range of 10-20 um
on each side of the cell. The largest potential-induced
displacements were found towards the cell base, whereas
virtually no motion was observed near the pipette tip,
‘The sensitivity to applied potential steps was 12 nm/mV
(Mammano et al., 1995).
Voltage-dependent fast transient currents, lasting 1 ms
or less, were present at onset and offset of the command
steps (Fig. 1A, top). Superfusion with 10 mM salicylate
reversibly abolished the transients (Fig. 1A, bottom) and
suppressed the motile responses. Subtracting the currents
obtained in the presence of salicylate from controls
eliminated the contribution to the transients from leakage
and ionic currents (Fig, 1B), Integration of the difference
current yielded a charge transfer with sigmoidal
dependence upon membrane potential (Fig. 1C) that
mirrored closely the voltage dependence of the cell
length changes (Ashmore, 1987). The dose/charge curve
measured during slow bath application of salicylate in
isolated cells had a Hill coefficient of 3.4, a half-maximal
dose of 3.9 mM and did not show appreciable voltage
dependence (Ashmore et al., 1995).
The cell membrane is known to be densely packed
Auditory periphery 7
with 12 nm protein particles which are believed to be
organized in tetramers (Kalinec et al., 1992) and have
been indicated as the molecular substrate of the outer
hair cell motor (Dallos et al., 1991). Cell length changes
would thus be associated with a reorganization of the
tetramers in the plane of the membrane powered by the
transmembrane electric field and revealed as fast charge
transients. A possible explanation for the effects of
salicylate and the voltage independence of its block is
that salicylate molecules, which possess both lipophilic
and hydrophilic properties, wedge through the mem-
brane and impede the rearrangement of the motor
proteins. In normal conditions the proteins are instead
free to drive the cell actin-spectrin cytoskeletal network
(cortical lattice), to which they are connected by 25 nm
long pillars (Holley & Ashmore, 1988), converting
surface into axial forces (Fig. 2)
Modelling
From a physico-mathematical point of view the organ
of Corti can be seen as a set of adjacent segments about
10m long formed by transversal portions of the
cochlear partition, each having the structure of a local
Resting
ae
Depolarized Salicylate
Fig. 2, Motor inner workings. (Left) Schematic drawing of an
outer hair cell. Horizontal arrow indicates displacement of the
stereocilia bundle in the excitatory (depolarizing) direction. The
cilia are connected by tip links. Inthe cochlea, mechanical input
to the stereocilia comes from the overlying tectorial membrane.
Stereocilia deflection stretches the tip links inducing the
opening of mechanosensitive cation channels attached to the
links. Channel gating modulates the resistance of the cell apical
membrane, resulting in the ‘generation of a receptor potential
(forward transduction). The cell responds by changing length
(vertical arrows, reverse transduction). (Right) Motor protein
particles inthe cell membrane are connected to the cytoskeleton
by short pillars (top). Depolarization induces a conformational
change in the particle distribution, diminishing the cel surface.
Interaction with the cytoskeleton converts surface forces to axial
forces applied along the cell length (botom left). The
transconformation is blocked by salicylate molecules
across the membrane (bottom right)
Scand Audiol 26, Sup 45