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Hair cells
Hair cells are the sensory receptors in the inner ear that
detect sound and head motion to begin the processes of
hearing and balance control. The defining feature of hair
cells is the hair bundle, the transduction organelle protruding
from their apical surface composed of ordered
arrays of stereocilia. Mechanical deflection of the hair
bundle, normally induced by physiological stimuli,
increases the open probability of mechanically gated
cation channels located at the tip of stereocilia. The
resulting depolarizing inward current generates a receptor
potential. The information encoded in this electrical
response is transmitted to the auditory or vestibular
afferent nerve fibres via the Ca2+-induced release of
neurotransmitter from the hair cell’s basal pole. In this
way sensory information is relayed to the brain enabling
us to perceive sound and maintain balance. In mammals,
hair cell loss causes irreversible balance and hearing
impairment because these sensory cells show very little or
no regenerative ability
Hair Cells
The auditory and the vestibular systems use hair
cells (HCs) as their sensory receptors. HCs are neu roepithelial cells characterised by the presence of
a bundle of microvilli-like structures that protrude
from their apical surface, called stereocilia. The
displacement of stereocilia, which is caused by
acoustic stimuli in the cochlea or head movement
in the vestibule, is converted into a depolarising
inward current by mechanoelectrical transducer
(MET) channels located at their tip. The depolarisa tion of HCs opens voltage-dependent Ca2+ channels
at their basolateral synaptic active zones, which
are functionally coupled to glutamate-containing
vesicles at specialised ribbon synapses. There is
also evidence for a nonquantal synaptic transmis sion at the vestibular HCs, likely involving direct
postsynaptic depolarisation by K+ exiting the cells.
In mammals, HC loss causes irreversible balance
and hearing impairment because these cells do not
regenerate
Single calcium channel (CaV1.3) activity recorded from mouse cochlear inner hair cells
Voltage-gated Ca2+ channels expressed in inner hair cells (IHCs) of the mammalian cochlea play a number of key physiological roles in their normal development and sound transduction (Housley et al. 2006, J Memb Biol 209:89-118). Ca2+ influx into IHCs occurs mainly (>90%) through Cav1.3 L-type Ca2+ channels (Platzer et al. 2000, Cell 102:89-97; Brandt et al 2003, J Neurosci 23:10832-40). Although some of the macroscopic biophysical properties of CaV1.3 Ca2+ channels are known, their elementary properties have yet to be determined in mammalian IHCs.
Single Ca2+ channel activity was recorded at body temperature from immature IHCs in cell-attached configuration using acutely dissected mouse organs of Corti. Voltage-dependent Ca2+ channels were investigated using Ba2+ in the patch pipette solution as the main charge carrier and Bay K 8644 to resolve the channel openings. Cell-attached recordings confirmed the presence of L-type Ca2+ channels, which showed a slope conductance of 39.0 pS and 17.6 pS in 70 mM and 5 mM Ba2+, respectively. The mean half maximum open probability (V1/2) significantly shifted from about ñ22 mV in 70 mM Ba2+ to ñ41 mV in 5 mM Ba2+. The voltage threshold for Ca2+ channel activation was also significantly less hyperpolarized in 70 mM Ba2+ than in 5 mM Ba2+. The maximum and the minimum open probability were: 0.120 and 0.005 in 5 mM Ba2+ and 0.042 and 0.002 in 70 mM Ba2+.
The present results are consistent with mammalian IHCs expressing a homogeneous population of voltage-dependent L-type Ca2+ channels containing the alpha1D (CaV1.3) subunit. The hyperpolarized activation of these Ca2+ channels indicate that they are likely to be active at the presumed resting membrane potential of IHCs, thus supporting spontaneous action potential activity characteristic of pre-hearing IHCs (Marcotti et al. 2003, J Physiol 552:743-761)
Properties of the single calcium channels CaV1.3 in mouse cochlear inner hair cells
Inner hair cells (IHCs) of the adult mammalian cochlea respond to sound stimuli with small and graded receptor potentials. Before the onset of hearing immature IHCs fire spontaneous Ca2+ action potentials. Both types of response lead to Ca2+ inflow through voltage-gated Ca2+ channels that causes neurotransmitter release at IHC ribbon synapses onto afferent fibres (Moser & Beutner 2000). More than 90% of the Ca2+ inflow occurs through the Cav1.3 L-type Ca2+ channels (Platzer et al. 2000), the single channel kinetics of which have yet to be determined.
METHODS: Single Ca channel activity was recorded in the “cell-attached” configuration (patch-clamp technique) from the mouse immature IHCs near body temperature. Voltage steps were applied from the holding potential of –70 mV. The patch pipette solution contained 5 or 70 mM of Ba2+ as the ion carrier and Bay K 8644 to better resolve the single channel openings.
RESULTS: L-type Ca channels showed a slope conductance of 39 pS and 17.6 pS in 70 and 5 mM Ba2+ respectively. The channel showed two open time constants at all voltages (at –30 mV the time constants were 0.4 and 4.9 ms with 5 mM Ba2+, and 0.4 and 1.5 ms with 70 mM Ba2+). Only the slower time constant was clearly voltage-dependent. Three closed states were found, of which only the longest was clearly voltage-dependent. Time-to-first opening distributions were fit by two time constants of which one was very fast (<1 ms).
CONCLUSIONS: IHCs L-type Ca channels show multiple gating states, some of which are voltage-dependent. The kinetics properties of the single Ca2+ channels recorded in the immature IHCs are consistent with the ribbon synapses sustaining a fast and precise release onto the afferent terminal (Goutman and Glowatzki 2007)
Properties of the Cav1.3 calcium channels expressed in mouse cochlear inner hair cells synapses
Cochlear inner hair cells express CaV1.3 Ca channels characterized by a very lnegative voltage-activation threshold and a strictly voltage-dependent open probabilit
Signal transmission in mature mammalian vestibular hair cells
The maintenance of balance and gaze relies on the faithful and rapid signaling of head movements to the brain. In mammals, vestibular organs contain two types of sensory hair cells, type-I and type-II, which convert the head motion-induced movement of their hair bundles into a graded receptor potential that drives action potential activity in their afferent fibers. While signal transmission in both hair cell types involves Ca2+-dependent quantal release of glutamate at ribbon synapses, type-I cells appear to also exhibit a non-quantal mechanism that is believed to increase transmission speed. However, the reliance of mature type-I hair cells on non-quantal transmission remains unknown. Here we investigated synaptic transmission in mammalian utricular hair cells using patch-clamp recording of Ca2+ currents and changes in membrane capacitance (ΔCm). We found that mature type-II hair cells showed robust exocytosis with a high-order dependence on Ca2+ entry. By contrast, exocytosis was approximately 10 times smaller in type-I hair cells. Synaptic vesicle exocytosis was largely absent in mature vestibular hair cells of CaV1.3 (CaV1.3−/−) and otoferlin (Otof−/−) knockout mice. Even though Ca2+-dependent exocytosis was small in type-I hair cells of wild-type mice, or absent in CaV1.3−/− and Otof−/−mice, these cells were able to drive action potential activity in the postsynaptic calyces. This supports a functional role for non-quantal synaptic transmission in type-I cells. The large vesicle pools in type-II cells would facilitate sustained transmission of tonic or low-frequency signals. In type-I cells, the restricted vesicle pool size, together with a rapid non-quantal mechanism, could allow them to sustain high-frequency phasic signal transmission at their specialized large calyceal synapses
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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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