A large-conductance calcium-selective mechanotransducer channel in mammalian cochlear hair cells.
ABSTRACT Sound stimuli are detected in the cochlea by opening of hair cell mechanotransducer (MT) channels, one of the few ion channels not yet conclusively identified at a molecular level. To define their performance in situ, we measured MT channel properties in inner hair cells (IHCs) and outer hair cells (OHCs) at two locations in the rat cochlea tuned to different characteristic frequencies (CFs). The conductance (in 0.02 mM calcium) of MT channels from IHCs was estimated as 260 pS at both low-frequency and mid-frequency positions, whereas that from OHCs increased with CFs from 145 to 210 pS. The combination of MT channel conductance and tip link number, assayed from scanning electron micrographs, accounts for variation in whole-cell current amplitude for OHCs and its invariance for IHCs. Channels from apical IHCs and OHCs having a twofold difference in unitary conductance were both highly calcium selective but were distinguishable by a small but significant difference in calcium permeability and in their response to lowering ionic strength. The results imply that the MT channel has properties possessed by few known candidates, and its diversity suggests expression of multiple isoforms.
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ABSTRACT: Adaptation in a vestibular organ, the bullfrog's sacculus, was studied in vivo and in vitro. In the in vivo experiments, the discharge of primary saccular neurons and the extracellular response of saccular hair cells were recorded during steps of linear acceleration. The saccular neurons responded at the onset of the acceleration steps, then adapted fully within 10-50 msec. The extracellular (microphonic) response of the hair cells adapted with a similar time course, indicating that the primary sources of the neural adaptation are peripheral to the afferent synapse--in the hair cell, its mechanical inputs, or both. Evidence for hair cell adaptation was provided by 2 in vitro preparations: after excising the sacculus and removing the accessory structures, we recorded either the extracellular hair cell response to displacement of the otolithic membrane or the intracellular hair cell response to hair bundle displacement. In both cases the response to a step stimulus adapted. The adaptation involved a shift in the displacement-response curve along the displacement axis, so that the cell's operating point was reset toward the static position of its hair bundle. This displacement shift occurred in response to both depolarizing and hyperpolarizing stimuli. Its time course varied among cells, from tens to hundreds of milliseconds, and also varied with the concentration of Ca2+ bathing the apical surfaces of the hair cells. Voltage-clamp experiments suggested that the displacement shift does not depend simply on ion entry through the hair cell's transduction channels and can occur at a fixed membrane potential. The possible role of the displacement-shift process in the function of the frog's sacculus as a very sensitive vibration detector is discussed.Journal of Neuroscience 09/1987; 7(9):2821-36. · 6.91 Impact Factor
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ABSTRACT: Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.Cell 04/2003; 112(6):819-29. · 31.96 Impact Factor
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ABSTRACT: Until recently the responses of the mechanosensitive hair cells of the cochlea have been inferred from their morphology, morphological relationships with other structures in the cochlea, and by indirect electrophysiological measurements. With the advent of techniques for making intracellular recordings from hair cells in the cochleas of anaesthetised mammals it has been possible to measure the responses of hair cells to acoustic stimulation and to assess their roles in sensory transduction in the cochlea. Intracellular recordings of the responses of inner and outer hair cells in the basal turn of the guinea-pig cochlea show that they differ considerably from each other. The receptor potentials of inner hair cells are larger, predominantly depolarizing to low frequency tones and at their best frequencies (16-20 kHz) they generate depolarizing dc receptor potentials. Outer hair cells generate predominantly hyperpolarizing potentials to low frequency tones. They do not produce significant voltage responses at high frequencies except at high intensities when they generate slowly rising depolarizing potentials which are associated with loss of cochlear sensitivity. At low frequencies the receptor potentials of the inner hair cells phase lead those of the outer hair cell. Measurements of their frequency selectivity show that inner and outer hair cells are both sharply tuned. It is proposed that the responses of inner and outer hair cells are consistent with sensory and motor roles respectively in mechanoelectric transduction and that the outer hair cells are the site of an active mechanical process responsible for the frequency selectivity and sensitivity of the cochlea. Intracellular recordings from hair cells in the mouse cochlea maintained in vivo have provided a direct measure of the mechanosensitivity of cochlear hair cells (approximately 30 mV per degree of displacement of their stereociliary bundles) and indirect evidence that the transfer characteristics of the outer hair cells in vivo may be due to their mechanoelectrical interaction with the tectorial membrane. This is because the transfer characteristics of the inner and outer hair cells are similar in vitro in the absence of a tectorial membrane. Considerable importance is attributed to the shape of the transfer characteristics of the inner and outer hair cells. Changes in these characteristics during anoxia and following exposure to intense tones are associated with depolarization of the outer hair cells and loss of cochlear sensitivity and frequency selectivity. Current-voltage studies of hair cells in vivo show the inner and outer hair cells to be electrically nonlinear.(ABSTRACT TRUNCATED AT 400 WORDS)Hearing Research 02/1986; 22:199-216. · 2.54 Impact Factor