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Molecular Physiology of Auditory Hair Cells

Dominik Oliver

Auditory hair cells are the sensory cells that transduce acoustical (mechanical) stimuli into electrical signals which are then conveyed to the brain. In mammals, these cells are located in the organ of Corti, which is the sensory epithelium within the auditory part of the inner ear, the cochlea. The snail-shaped cochlea is a complex organ dedicated to mechanical processing of sound.

Uniquely among vertebrates, mammals are equipped with two quite different types of hair cells, the inner hair cells (IHCs) and the outer hair cells (OHCs). While IHCs are the proper receptor cells of hearing and are connected to the afferent nerves, OHCs serve to mechanically pre-amplify the mechanical vibrations (i.e., sound) that reach the inner ear. This process, termed ‘cochlear amplification’, is pivotal to the exquisite sensitivity and the high frequency resolution of mammalian hearing.

Dysfunction or loss of OHCs is the most frequent cause of hearing loss and deafness. How can sensory cells provide mechanical amplification? It is now known that OHCs can rapidly alter their shape (rapid elongation/contraction cycles) in response to changes of the electrical membrane potential. This voltage-driven movement termed electromotility appears to be the motor that drives cochlear amplification.

We are interested in understanding the molecular mechanisms of electromotility. Because it must operate at acoustic frequencies (tens of kilohertz), electromotility ist incredibly fast, in fact much more rapid than other cellular movements, e.g. those that underlie muscular contraction. Accordingly, the mechanism underlying electromotility is also quite different from myosin-based motility: it is intrinsic to the outer hair cell’s membrane and is generated by a membrane protein termed prestin. Prestin appears to sense membrane potential and to change its molecular dimensions response to voltage changes. Current models suggest that aggregate conformational changes of a large population of these transmembrane proteins within the plasma membrane of OHCs drive electromotility and thus cochlear amplification.

We focus on the following topics in hair cell physiology:

1. Function and structure of the outer hair cell motor protein, prestin.

2. Transport mechanisms of prestin-related anion transporters (i.e. SLC26-transporters)

3. Biophysical properties and physiological role of ion channels (in particular K+-channels) in auditory hair cells.