Hair cells transduction

Hair cells are the sensory cells of the auditory and vestibular systems 835 Hair cells are exposed to unusual extracellular fluids and potentials 836 Mechanical transduction depends on activation of ion channels linked to extracellular and intracellular structures 836 Some of the molecules responsible for hair-cell transduction have been identified 838... 

Hair cells are specialized mechanoreceptors located in the inner ear these cells transduce mechanical forces transmitted by sound and head movement, and permit an organism to sense features of the external world. Well-characterized biophysically, a molecular description of hair-cell transduction has finally begun to emerge. 

The protein NompC is a TRP channel and appears to be the major transduction channel in fly bristles [6], Bristle mechanotransduction resembles hair-cell transduction remarkably in its speed, polarity and adaptation [6], suggesting the possibility of a close evolutionary relationship between these mechanoreceptors. NompC is not the only... 

FIGURE 51 -B Hair-cell transduction. Only two stereocilia out of a bundle are shown. The transduction channel (yellow) is gated by the tip link. At rest, channels spend 10% of the time open. An excitatory deflection moves the bundle towards the taller stereocilia increased tension in the tip link leads to channel opening and entry of K+ and Ca2+. Moving the bundle towards the shorter stereocilia is inhibitory this movement causes tension in the tip link to drop, and the channels then close. 

Some of the molecules responsible for hair-cell transduction have been identified. A few key molecules, some already described, have been identified as part of the transduction complex (Fig. 51-6). Myosin molecules clearly play essential roles, and hair cells express a variety of myosin isoforms. Because it is located at the tips of the stereocilia, near the tip-link anchors, myosin-1 c is the best candidate for the adaptation motor. Selective inhibition of a sensitized myosin- lc mutant with an ADP analog proved that this myosin participates in adaptation [14], although contribution by other myosins has yet to be ruled out. For example, mice with near-null mutations in myosin-7a have defects in auditory transduction that are consistent with alterations in the adaptation machinery, suggesting a central role for this myosin too [15]. 

Figure 32.34. Model for Hair-Cell Transduction. When the hair bundle is tipped toward the tallest part, the tip link pulls on and opens an ion channel. Movement in the opposite direction relaxes the tension in the tip link, increasing the probability that any open channels will close. [Adapted from A. J. Hudspeth. Nature 341 (1989) 397.j...

The most important molecules so far identified from this screen include a likely transduction channel, an extracellular molecule that could gate channels, and several molecules known to be important for axonemal structure and function. Although the set of molecules is less complete than that identified for C. elegans touch receptors, the diversity of mechanotransduction in Drosophila and the apparent similarity of these receptors to those in vertebrates, including hair cells (see below), demonstrates the significance of this model system. 

Hair cells are the sensory cells of the auditory and vestibular systems. Hair cells are the sensory cells of the internal ear, essential for the senses of sound and balance. The hair cell s transduction apparatus, the molecular machinery that converts forces and displacements into electrical responses, can respond to mechanical stimuli of less than 1 nm in amplitude, and of tens or even hundreds of kilohertz in frequency. Indeed, our hearing is ultimately limited by Brownian motion of water molecules impinging on the transduction apparatus. 

Even though well-characterized at a biophysical level, the mechanical transduction mechanism of hair cells is still not fully understood in molecular terms. This discrepancy is in part due to the extreme scarcity of hair cells instead of the millions or even hundreds of millions of receptor cells that the olfactory and visual systems possess, only a few tens of thousands of hair cells are found in the internal ears of most vertebrate species. The small number of hair cells and the direct transduction mechanism has greatly impeded molecular biological and... 

Transduction channels do not remain open, even if a deflection is maintained using two independent processes, the hair cell adapts to a sustained mechanical stimulus [12]. Rapid channel reclosure (sometimes called fast adaptation) occurs on a time-scale of a few milliseconds... 

FIGURE 51-4 Fast adaptation by hair cells. After a positive (excitatory) deflection, Ca2+ enters transduction channels, binds to a site at the channel, yanking the channel shut. The movement of the channel s gate increases tension in the tip link, and the bundle is moved in the negative direction. 

Recent experiments have suggested that the tip link, a complex of two or three braided glycoprotein filaments [19], may be made in part from cadherin-23, a Ca2+-dependent cell-adhesion molecule [20], Moreover, cadherin-23 can interact directly or indirectly with myosin- lc, suggesting that these two molecules form part of the transduction complex in hair cells [20]. 

The surprise is that genes clearly involved in mechano-transduction have not yet been identified by the deafness-gene approach. Clearly disruption of hair-cell function at many levels can lead to deafness, so it is expected that deafness genes include those involved in inner-ear development, in ion balance in the endolymph, and in structural integrity of hair cells. Examination of deafness genes in zebrafish has been particularly thorough, however, and... 

The tectorial membrane rests at the top of the organ of Corti, and the basilar membrane forms the base. Two types of hair cells are found along the basilar membrane. There are three rows of outer hair cells and one row of inner hair cells. The outer hair cells form part of the mechanical system of the cochlear partition, while the inner hair cells provide transduction from mechanical motion into neural firing patterns. There are about 30,000 nerve fibers in the human ear. The vast majority are afferent fibers that conduct the inner hair cell neural pulses towards the brain approximately 20 fibers are connected to each of the 1,500 inner hair cells. Approximately 1,800 efferent fibers conduct neural pulses from the brain to the outer hair cells [Pickles, 1988],... 

Figure 9.3. Model for the action of humic substances (HS) on plasma membrane-bound targets of a root hair cell. Besides the well-known effects on plasma membrane H+-ATPase (P) and carriers (C) of mineral nutrients, the envisaged alteration of membrane lipid environment and the possible interaction with an hypothetical membrane receptor (R) for humic molecules which allows transduction of the signal for induction and expression of genes involved in nutrient uptake and root hair development are also presented.

The presence of these tip links suggests a simple mechanical model for transduction by hair cells (Figure 32.34). The tip links are coupled to ion channels in the membranes of the stereoeilia that are gated by mechanical stress. In the absence of a stimulus, approximately 15% of these channels are open. When the hair bundle is displaced toward its tallest part, the stereoeilia slide across one another and the tension on the tip links increases, causing additional channels to open. 

J.O. Pickles andD.P. Corey. 1992. Mechanoelectrical transduction by hair cells Trends Neurosci. 15 254-259. 

The human inner ear is embedded in the temporal bone and houses the sensory epithelia of the cochlea and vestibular apparatus (Fig. 1). The sensory epithelia contain hair cells which transduce the stimulus of sound or motion into nerve impulses. Hair cells are equipped with an apical mechano-sensitive apparatus made up by three rows of actin-containing stereocilia of increasing length. Displacement of the stereocilia towards the longest row opens (gates) mechano-electrical transduction channels, whereas deflection into the opposing direction closes the channels [12],... 

Since the inner ear is an anatomically complex structure with specialized epithelial hair cells, the use of cell lines as simplified models in ototoxic research is limited mostly to the analysis of heterologously expressed proteins. As the molecular identity of many hair cell protein complexes has not completely been resolved yet (e.g., the transduction channels), many hair cell components relevant to ototoxicity cannot be reconstituted in cultured cells adequately [79]. 

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