OHCs: physiology

The Cochlear amplifier

At the beginning of the 1980s, our understanding of cochlear physiology came to an apparent contradiction: on one hand, neurophysiologists described a remarkable frequency selectivity at the leel of the auditory nerve. On the other hand, Bekesy's traveling wave theory made it difficult to imagine the cochlea as anything other than a passive filter, which was unable to to provide this amazing selectivity. This was despite the description, in 1948, of 'active mechanical filters' by a physicist named Gold.

Two different results dispelled the idea of a 'passive' cochlea: the discovery of otoacoustic emissions (OAEs), and the precise measurement of the vibrations of the basilar membrane in response to a pure tone, which demonstrated that frequency tuning occurred before the signal reached the auditory nerve.

A double transduction mechanism

In the same way as for the IHCs, acoustic vibrations cause motion of the stereocilia of the OHCs, which in turn causes a modulation in cellular potential. In the case of a pure tone, the stereocilia oscillate in a sinusoidal manner, which induces a succession of depolarisations and repolarisations of the OHCs. This electrical activity can be recorded in the laboratory, and is called the cochlear microphonic potential. In contrast to what happens in the IHCs, variations in the OHC's potential causes them to change shape. When they depolarise they become shorter, and become longer at repolarisation. These changes in the length of the OHCs are caused by voltage-sensitive changes in the shape of a protein that is very abundant in the cellular membrane: prestin. OHCs therefore have a role of oscillators that cause localised amplification of the basilar membrane. This property increases cochlear sensitivity by around 60 dB and increases its ability to differentiate between similar frequencies. The OHCs are therefore of vital importance for auditory function.

OHC active mechanism and tuning

For a pure tone, the active mechanism amplifies the vibrations of the basilar membrane by around 50 dB (this increases cochlear sensitivity) over a narrow portion of the organ of Corti. Two similar frequencies are therefore able to activate two distinct cochlear regions, allowing them to be distinguished from each other (this is known as frequency selectivity). Frequency tuning depends closely on the electromotile properties of the OHCs and is maintained at the level of the fibers of the auditory nerve (where it is transmitted via the inner hair cells).

Electromotility

Electromotility was discovered in 1983 using explanted OHCs. Since then, the contractile property of the OHCs has been well studied. It is a rapid mechanism (which can follow high frequencies to at least 20 kHz), which does not depend on calcium or ATP, meaning that it has no direct energy consumption (although the general physiology of the OHC does require a dependable source of ATP-based energy).

Contraction of the OHCs is the result of the sum of the contraction of the 'motor' elements lovated in the lateral wall of the OHCs. Today, it is thought that depolarising the OHCS (influx of K⁺ upon sound stimulation) modifies the conformation of prestin, a transmembrane protein, which plays a motor role (see animation below). This concept has recently been clearly confirmed by cloning the prestin gene and deleting it, causing an abolition of electromotility.

S. Blatrix, after G. Rebillard

Depolariation of the OHCs causes the inward displacement of anions, probably Cl^-, from their linkage site with prestin into the cytoplasm.
This charge displacement causes the protein to shorten, which translates as a contraction of the OHC.
The opposite occurs when the OHC repolarises - the anions link to prestin, causing a the OHC to stretch.

Note: Alongside electromotility, explanted OHCs have revealed various other contratile properties such as slow calcium-dependant contraction, which modulates electromotility and is operated via the medial efferent system. Currently, the physiological properties of this medial efferent control of the OHCs are unclear: they may be involved in a cochlear protection, or attenuation of the active mechanisms involved in the cocktail party effect.

Lateral wall and intracellular complex of an outer hair cell

The electromotile properties of the OHCs are correlated with the characteristic structure of their lateral wall (the portion of the membrane from the cuticular plate to the nucleus) and the associated complex of intracellular organelles.

	The vesicles of the endoplasmic reticulum are aligned between the lateral wall and the mitochondria. The number of these structures varies from the base (1 row of vesicles: see right) to the apex of the cochlea (4 or 5 row: see left). Between the first (or only) row of vesicles and the plasma membrane, columns and other microstructures can been seen, which form sub-membrane cytoskeletal complexes (see diagram, below). TEM images: R. Pujol and M. Lenoir / Scale: 100 nm
S. Blatrix, adapté d'Ashmore et Holley	Schematic arrangement of the lateral wall of an OHC and the intracellular cytoskeleton. The three components of the intracellular complex are clearly defined between the membrane (turquoise, partially raised) and the first reticular vesicle (blue): actin filaments (red) encircle the OHCs, probably in a helical, spring-like shape, with a spacing of around 100 nm (see the diagram of the whole cell); spectrin filaments (or fimbrin, in yellow), arranged longitudally and spaced at around 50 nm intervals; columns (purple), which lie perpendicular to the membrane. Figure: Membrane laterale et complex sous-membranaire de la CCE ==>  Lateral wall and sub-membrane complex of the OHC.
Le Grimellec, Lenoir, Pujol et al.	Near-field microscopy Outer surface of the lateral wall of an OHC. On this µm² of membrane, a distinctive arrangement of membrane proteins can be seen: the slanted lines indicate protein alignment, spaced at around 50 nm (blue lines) and 100 nm (red lines). See the diagram above. These proteins, which appear to represent the transmembrane portion of the columns, and could be the 'motors', have a conical shape and often have an apparent central pore.