[Show abstract][Hide abstract] ABSTRACT: In an attempt to expand on the pioneering work of the latter part of the last century, a feverish quest continues to uncover the events that lead to cochlear ampli.cation in mammals. The role of the OHC is certainly paramount, and we now have identified many of its membrane constituents that form the basis of the cell's unique contribution. As this review intimates, the motor protein prestin and its interaction with other players within and beneath the plasma membrane drive the cell's augmentation of mammalian hearing acuity. Nevertheless, we are far from understanding the full complement of cellular elaborations that define the cell's mechanical capabilities, Surely, the next quarter century will tell more.
Full-text · Article · Jan 2006 · Journal of Membrane Biology
[Show abstract][Hide abstract] ABSTRACT: Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes in membrane potential.
This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltage-sensitive motor molecule
recently identified as the membrane protein prestin. Here, we show that voltage sensitivity is conferred to prestin by the
intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well
as the characteristic nonlinear charge movement (“gating currents”) driving the underlying structural rearrangements of the
protein. The results support a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule
and thus trigger the conformational changes required for motility of OHCs.
[Show abstract][Hide abstract] ABSTRACT: Outer hair cell (OHC) electromotility, which powers the cochlear amplifier, develops at a later stage of hearing ontogeny. There has been speculation whether efferents play a necessary role in directing or achieving OHC maturation in mammals. In this study, we examine whether the development of OHC motility depends on the establishment of efferent innervation of the cells' synaptic pole by measuring electromotility of OHCs grown in cultures, deprived of efferent innervation. Tissue cultures of the organ of Corti were prepared from the cochleas of newborn gerbils. Solitary OHCs were obtained from 4- to 15-d-old cultures by enzymatic digestion and mechanical trituration. Length changes evoked by transcellular electrical stimulation were detected and measured with a photodiode sensor. Results show that OHCs develop electromotility between 6 and 13 d in culture without the presence of efferent innervation. The timetable for the onset of OHC electromotility is comparable with that in vivo. This demonstrates that the ontogeny of OHC electromotility is an intrinsic process that does not require the influence of efferent innervation.
Preview · Article · Jun 1997 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
[Show abstract][Hide abstract] ABSTRACT: The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond with a somatic shape change to alterations in their membrane potential, and this electromotile response is believed to provide mechanical feedback to the basilar membrane. We examine the effects of ACh on electromotile responses in isolated OHCs and attempt to deduce the mechanism of ACh action. Axial electromotile amplitude and cell compliance increase in the presence of the ligand. This response occurs with a significantly greater latency than membrane current and potential changes attributable to ACh and is contemporaneous with Ca2+ release from intracellular stores. It is likely that increased axial compliance largely accounts for the increase in motility. The mechanical responses are probably related to a recently demonstrated slow efferent effect. The implications of the present findings related to commonly assumed efferent behavior in vivo are considered.
No preview · Article · Apr 1997 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
[Show abstract][Hide abstract] ABSTRACT: The cochlear outer hair cell (OHC), which plays a crucial role in mammalian hearing through its unique voltage-dependent length change, has been established as a primary target of the ototoxic activity of aminoglycoside antibiotics. Although the ototoxicity eventually leads to hair cell loss, these polycationic drugs are also known to block a wide variety of ion channels such as mechanotransducer channels, purinergic ionotropic channels and nicotinic ACh receptors in acute preparations. The OHC motor protein prestin is a voltage-sensitive transmembrane protein which contains several negatively charged residues on both intra- and extracellular surface. The acidic sites suggest that they may be susceptible to polycationic- charged aminoglycoside binding, which could result in a disruption of somatic motility. We attempted to examine whether aminoglycosides such as streptomycin and gentamicin could affect the mechanical response of OHCs. Solitary OHCs isolated from adult gerbils were used for the experiments. Somatic motility and nonlinear capacitance were measured under the whole-cell voltage-clamp mode. Streptomycin and gentamicin were applied extracellularly or intracellularly. Results show that streptomycin and gentamicin, for the concentration range between 100 µM and 1 mM, did not affect somatic motility or nonlinear capacitance. The result suggests that although streptomycin and gentamicin can block mechanotransduction channels as well as ACh receptors in hair cells, they have no immediate effect on OHC somatic motility.