How to build an inner hair cell: challenges for regeneration.

During their development inner hair cells (IHCs), the primary sensory receptors in the mammalian cochlea, undergo a meticulously orchestrated series of changes in the expression of ion channels and in their presynaptic function. This review considers what we currently know about these changes in IHCs of mice and rats, which start hearing 10-12 days after birth. Just after terminal mitosis the IHCs are electrically quiescent and functionally isolated, expressing only small and slow outward K(+) currents in their basolateral membranes. By the first postnatal week the cells have acquired inward Ca(2+) and Na(+) currents that enable them to fire spontaneous action potentials at a time when the cochlea can not yet be stimulated by sound. These action potentials may be essential for normal development and survival of the IHCs themselves and of the afferent nerve fibres that synapse with them. At the onset of hearing the transition to a functionally mature sensory receptor comes about by the expression of a large and fast BK current, I(K,f), a KCNQ4 current, I(K,n), and by changes in the exocytotic machinery. Some implications of this complex developmental programme for the ideal of hair-cell regeneration in the mature mammalian cochlea are discussed.