1,720,999 research outputs found
Regulation of outer hair cell cytoskeletal stiffness by intracellular Ca2+: underlying mechanism and implications for cochlear mechanics
No full textTwo Ca2+-dependent mechanisms have been proposed to regulate the mechanical properties of outer hair cells (OHCs), the sensory-motor receptors of the mammalian cochlea. One involves the efferent neurotransmitter, acetylcholine, decreasing OHC axial stiffness. The other depends on elevation of intracellular free Ca2+ concentration ([Ca2+](i)) resulting in OHC elongation, a process known as Ca2+-dependent slow motility. Here we provide evidence that both these phenomena share a common mechanism. In whole-cell patch-clamp conditions, a fast increase of [Ca2+](i) by UV-photolysis of caged Ca2+ or by extracellular application of Ca2+-ionophore, ionomycin, produced relatively slow (time constant similar to20 s) cell elongation. When OHCs were partially collapsed by applying minimal negative pressure through the patch pipette, elevation of the [Ca2+](i) up to millimole levels (estimated by Fura-2) was unable to restore the cylindrical shape of the OHC. Stiffness measurements with vibrating elastic probes showed that the increase of [Ca2+], causes a decrease of OHC axial stiffness, with time course similar to that of the Ca2+-dependent elongation, without developing any measurable force. We concluded that, contrary to a previous proposal, Ca2+-induced OHC elongation is unlikely to be driven by circumferential contraction of the lateral wall, but is more likely a passive mechanical reaction of the turgid OHC to Ca2+-induced decrease of axial stiffness. This may be the key phenomenon for controlling gain and operating point of the cochlear amplifier. (C) 2003 Elsevier Science Ltd. All rights reserved
Purinergic control of intercellular communication between Hensen's cells of the guinea pig cochlea
Full text linkHensen's cells in the isolated cochlea were stimulated by extracellular adenosine 5 ' -triphosphate (XTP) applied to their endolymphatic surface while changes in membrane current and intracellular calcium concentration ([Ca(2+)](i)) were measured simultaneously. The response consisted of (i) an initial rapid inward current accompanied by elevation of the [Ca(2+)](i), (ii) a more slowly rising inward current accompanied by a rise of the [Ca(2+)](i) and (iii) a slowly developing reduction of input conductance
Frequency dependence of electrical coupling in Deiters' cells of the guinea pig cochlea
No full textImmunolabeling with antibodies against connexins 26 and 30 shoved that. in the guinea pig cochlea, supporting Deiters' cells are massively interconnected and form an orderly network within the organ of Corti. In paired patch-clamp recordings the coupling ratio (CR) of adjacent Deiters' cells at the apex of the cochlea (similar to0.31) was 3-fold smaller than in isolated cell pairs due to shunting afforded by multicellular connectivity. With sinusoidal current stimuli the delay in signal propagation between adjacent cells increased with increasing frequency whereas the amplitude did not change significantly up to 200 HZ (corner frequency F-c similar to220 Hz). Depolarizing voltage commands applied to an outer hair cell (OHC) elicited outward potassium currents in the OHC and inward currents in the abutting Deiters, cells, supplying direct evidence for potassium buffering in the organ of Corti. Computational analysis indicates that electrical signals injected into a Deiters' cell are transmitted across a network segment spanning 8 cell diameters. Thus electrical coupling in the organ of Corti is unlikely to influence the selectivity of frequency filtering performed mechanically by the mammalian cochlea
Action of 2,3-butanedione monoxime on capacitance and electromotility of guinea pig cochlear outer hair cells
Full text link1. Whole-cell patch-clamp recordings were obtained from isolated cochlear outer hair cells (OHCs) while applying 2,3-butanedione monoxime (BDM) by pressure. BDM (5 mM) shifted the range of voltage sensitivity of membrane capacitance and cell length in the hyperpolarised direction by -49.6 +/- 4.0 mV (n = 12; mean +/- S.E.M.), without appreciable effects on membrane conductance. The shift was completely reversible and dose dependent, with a Hill coefficient of 1.8 +/- 0.4 and a half-maximal dose of 3.0 +/- 0.8 mM (values +/- S.D).
2. The shift of the capacitance curve was also reproducible in cells whose natural turgor had been removed. BDM had no detectable effect on the capacitance of Deiters' cells, a non-sensory cell type of the organ of Corti.
3. The effect of BDM on membrane capacitance was faster than that of salicylate. At similar saturating concentrations (20 mM), the time constant of the capacitance changes was 1.8 +/- 0.3 s (n = 3) for salicylate and 0.75 +/- 0.06 s (n = 3) for BDM. The recovery periods were 13 +/- 1 s and 1.7 +/- 0.4 s, respectively (means +/- S.E.M.).
4. The effect of BDM, a known inorganic phosphatase, was compared to the effects of okadaic acid, trifluoperazine and W-7, which are commonly used in studies of protein phosphorylation. Incubation of OHCs with okadaic acid (1 muM, 30-60 min) shifted the voltage sensitivity of the membrane capacitance in the hyperpolarised direction. Incubation with trifluoperazine (30 muM) and W-7 (150 muM) shifted it in the opposite, depolarised direction. BDM induced hyperpolarising shifts even in the presence of W-7.
5. Simultaneous measurement of membrane capacitance and intracellular free Ca2+ concentration ([Ca2+](i)) showed that BDM action on OHC voltage-dependent capacitance and electromotility is not mediated by changes of [Ca2+](i).
6. Our results suggest that: (a) the effects of BDM are unrelated to its inorganic phosphatase properties, cell turgor conditions or Ca2+ release from intracellular stores; and (b) BDM may target directly the voltage sensor of the OHC membrane motor protein
The membrane based mechanism of cell motility in cochlear outer hair cells
Full text linkThe sensitivity of the mammalian inner ear is extraordinary. At the threshold of hearing, the incoming sound produces vibrations inside the organ of Corti that are of the same order of magnitude or less than the thermal noise motion (Hudspeth, 1989, 1997; Dallos, 1996). Such sensitivity is achieved through an energy-dependent process commonly referred to as “cochlear amplifier,” i.e., the cycle-by-cycle amplification of the intracochlear vibrations that neutralizes viscous losses by positive mechanical feedback (Patuzzi and Robertson, 1988;Ashmore and Kolston, 1994; Kolston, 1995). The mechanical feedback force that makes the amplification possible is thought to be provided by cochlear outer hair cells (OHCs), a class of specialized sensorimotor cells hosted within the organ of Corti (Lim and Kalinec, 1998; Nobili et al., 1998). Direct support to the feedback hypothesis comes from the fact that OHCs posses a unique ability to change significantly their shape in response to electrical stimulation (Brownell et al., 1985; Kachar et al., 1986), a phenomenon called electromotility
Exogenous ATP induces rapid release of intracellular calcium at the base of the hair bundle in outer hair cells
No full textWe used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca2+ concentration ([Ca2+]i) evoked by focal applications of extracellullar ATP to the hair bundle of outer hair cells (OHCs) - the sensory-motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca2+]i. After an initial entry of Ca2+ through the apical membrane, a second and larger, InsP3-gated, [Ca2+]i surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca2+ release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen’s body. Using confocal immunofluorescence microscopy, we showed that InsP3 receptors share this location. Consistent with a Ca2+-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca2+]i rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca2+-clearance power of the stereocilia and transiently elevates [Ca2+]i at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechano-transduction
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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