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The Auditory Periphery 2 – Hair Cell Structure and Transduction

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The Auditory Periphery 2 – Hair Cell Structure and Transduction The Auditory Periphery 2 – Hair Cell Structure and Transduction Dr. Elisabeth Glowatzki 955-3877 [email protected] 521 Traylor Building Websites: Promenade ‘round the cochlea (http://www.iurc.montp.inserm.fr/cric/audition/english/start.htm) Auditory Animations, Univ. of Wisconsin (http://www.neurophys.wisc.edu/animations/) Texts (at Welch or Eisenhower): From Sound to Synapse, C. D. Geisler, New York: Oxford Univ. Press, 1998 An Introduction to the Physiology of Hearing, J. O. Pickles, New York: Academic Press, 1982 Fundamentals of Hearing: An Introduction (3rd ed.), W. A. Yost, San Diego: Academic Press, 1994 Hackney CM, Furness DN (1995) Mechanotransduction in vertebrate hair cells: structure and function of the stereociliary bundle. Am. J. Physiol. 268:C1-C13. 1 The Organ of Corti Stephan Blatrix Overview over the organ of Corti One row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), both with stereocilia bundles. The IHCs are flask-shaped, the OHCs are rod- shaped. Both have stereocilia bundles at the apex and synapses at the base. The OHC stereocilia bundles contact the tectorial membrane, the IHC stereocilia bundles seem not to contact the tectorial membrane. Innervation: 1. IHCs make 95% of afferent glutaminergic synapses (blue). 2. OHCs make 5 % of afferent synapses; their function is unknown (green). 3. OHCs make efferent cholinergic (ACh-activated synapses (red). 4. During development IHCs make have cholinergic synapses (not shown). 2 Cross sections of Organ of Corti of guinea pig. Upper from apex, lower from base of cochlear spiral. R. Pujol. Two histological sections of the organ of Corti, one apical, one basal. One row of IHCs, three rows OHCs, supporting cells around the IHC and under the OHCs. The tectorial membrane always lifts up from the stereocilia in histological sections (due to the change in ionic environment?). 3 Deflection of the Stereocilia Bundles Transduction process: Stereocilia of IHCs and OHCs are deflected against the tectorial membrane, when the basilar membrane is set in motion. 4 Transduction and Synaptic Transmission at the Inner Hair Cell Stephan Blatrix How is the transduction signal transmitted to the brain? Sound sets the basilar membrane in motion. The stereocilia bundles are deflected against the tectorial membrane. The hair cell is depolarized by K+ influx at the apex of the hair cell through transduction channels. The transduction current generates a receptor potential. Depolarization of the hair cell opens voltage gated Ca2+-channels at the base of the hair cell and induces transmitter release. Vesicles filled with glutamate fuse with the synaptic membrane in a Ca 2+ - dependent manner. Glutamate in the synaptic cleft activates glutamate receptors on the afferent fiber terminal and induces excitatory postsynaptic potentials (EPSPs). The EPSPs activate action potentials that travel down the auditory nerve. Deflection of the stereocilia bundles towards the biggest stereocilium induce an increase in the firing rate in auditory nerve fibers. Deflection in the opposite direction induce a reduction in firing rate. At rest (when no signal is applied to the hair cells), there is still some influx of K+ into the hair cell (about 10 % of the maximal current), some transmitter is released causing ‘spontaneous activity’ in the auditory nerve fibers. 5 Conductances in the Lateral Wall of the Hair Cells Shape the Receptor Potential g transduction g (ATP) The receptor potential is shaped by the transduction current and a number of basolateral conductances, some of which are illustrated here in this figure. For example voltage-gated potassium conductances g Kv, Ca2+-dependent potassium conductances, ligand-gated conductances (ATP, Acetylcholine) etc. can impact the shape of the receptor potential. 6 Hair Cell & Hair Bundle Examples IHC OHC Turtle VHC Turtle VHC Bullfrog VHC Hair cell and hair bundle examples in electron-microscopic images. Note: in vivo, the stereocilia and kinocilium (the tallest stereocilium in vestibular hair cells) are rigid and upright (not curved, as shown particularly in the turtle vestibular hair cell bundles due to fixation). Observations: • Pipe-organ arrangement in vestibular hair cell hair bundles (mammalian and non- mammalian) and cochlear hair bundles of non-mammalian vertebrates. • Staircase arrangement in mammalian cochlear hair bundles (3-4 rows). • Axis of bilateral symmetry • Tapered base of stereocilia • Tilted inward • Number of stereocilia per bundle varies widely • Chick cochlear hair bundles: 50-300 • Across species, number of stereocilia decreases from base (HF) to apex (LF). • Stereocilium length and cell size increases from base to apex. • Kinocilia in VHC end as a bulb or may be very large. They seem to anchor the hair bundle to the overlying (otolithic) membrane. They are present in cochlear hair cells only during development. •An unansered question: What is the functional significance of differences in bundle shape? • Stereocilia act as rigid, pencil-like rods that bend at the base about the rootlet. Images: IHC/OHC (Promenade website), Turtle VHC (Ellengene Peterson, unpublished), Frog VHC (Strassmaier & Gillespie, 2002) 7 Stereocilium Structure Tilney et al. (1983) Tilney et al. (1980) Stereocilia are composed of a paracrystalline array of tightly (hexagonally) packed actin filaments with fimbrin cross-bridges. From alligator lizard (Tilney et al., 1980) • >3,000 actin filaments per stereocilium • ~18-30 form rootlet and extend into cuticular plate • The rootlet extends as a cone into the cuticular plate, increasing in diameter the farther it penetrates. Rootlet filaments are interconnected by fine 3-nm filaments and are presumably anchored by myosins among other proteins. •The actin core is suitable for myosin motility (Shepherd et al., 1990). Demembraned hair bundles were blotted and the movement of myosin coated beads were recorded. Myosin freely moved along the actin complex, seemingly uninhibited by the presence of fimbrin cross-bridges. This observation is critical for later discussion of myosin dependent adaptation. 8 Hair Bundle Motion Chick Tall Hair Cell Water-jet Stimulation 500 Hz 15º displacement Stroboscopic Lamp (Keith Duncan) This figure illustrates the movement of a stereocilia bundle of an isolated chick hair cell with fluid-jet, projecting a fluid wave onto the bundle. All stereocilia move together as a compact, stiff structure. 9 Tip Links Fettiplace, Ricci and Hackney, 2001 That the stereocilia bundle moves as a unit is due to the fact that a variety of linking proteins connect the stereocilia at different heights of the bundle. Tip-links are upward pointing links that connect the tip of shorter stereocilia to the shafts of adjacent stereocilia in the next taller row. Lateral links connect the shafts of adjacent stereocilia, and ankle links are specialized lateral links at the base of stereocilia (not shown here). Tip-links and lateral links are present in all hair bundles, but the extent of lateral link connectivity is highly variable (i.e. making horizontal connections along the entire length of the stereocilia shafts or making dense interconnections just below the stereociliary tips). The mechanotransducer channels are thought to be located close to the tip of the stereocilia, where the tip links contact the stereocilia. Deflection of the stereocilia bundle stretches the tip links or structures connected to the tip links and thereby opens transduction channels. 10 + 80 mV Mechanotransduction, based on studies by Corey, Crawford, Eatock, Fettiplace, Gillespie, Hudspeth and colleagues dV = 140 mV -60 mV Stephan Blatrix A very simple view on how mechanotransduction may work: the deflection of the stereocilia opens mechanotransduction channels, unspecific cation channels, permeable for Na, Ca and K. Due to the high K concentration in the endolymph, mainly K enters through the channel into the cell. The driving force is 140 mV. Proof for this theory will be presented later in this lecture after introducing methods how transduction currents have been recorded. 11 Transduction: Methods – 1 Frog Sacculus Corey & Hudspeth, 1983 Hudspeth & Corey, 1977 Recording from hair cells is no trivial task due to the unique fluid environment in vivo, the location of these cells within the bony labyrinth, and the necessity for micromechanical stimulation of the hair bundle. Here, we will describe several recording techniques. Single-electrode voltage recording (left) An epithelial preparation of the frog sacculus is pinned in an experimental chamber. Hair cells are penetrated using a single fine tipped microelectrode, measuring the cell’s membrane potential (note: not a voltage or current clamp configuration). A glass fiber holding the stereocilia bundle from the top is moving the bundle. Transepithelial preparation (right) An entire vestibular organ (most often the sacculus) is dissected and a portion of the otolithic membrane (overlying hair cells) is removed (OM). The preparation is mounted across a hole in a nonconducting surface (W). Thus, there are now two separate fluid chambers (simulating the in vivo environment). Electrodes are placed in the upper and lower chambers, and the apical and basolateral surfaces are clamped to 0 mV using a voltage-clamp circuit. Hair bundles are displaced en mass (SP); transduction currents flowing in through transduction channels and out through the basolateral surfaces are measured by the clamp circuit. The intracellular membrane potential is not clamped using this method, and
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