scholarly journals Synaptic contributions to cochlear outer hair cell Ca2+ homeostasis

2020 ◽  
Author(s):  
Marcelo J. Moglie ◽  
Diego L. Wengier ◽  
A. Belén Elgoyhen ◽  
Juan D. Goutman
Keyword(s):  
Outer Hair Cell ◽  
Control Function ◽  
Basolateral Membrane ◽  
Ryanodine Receptors ◽  
Outer Hair Cells ◽  
Synaptic Activity ◽  
Cochlear Function ◽  
Intracellular Ca ◽  
Regulation Mechanisms ◽  
Different Origins

AbstractFor normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca2+ levels. Influx of Ca2+ occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca2+ influx have been poorly explored: voltage-gated Ca2+ channels (VGCC) at synapses with type II afferent neurons, and α9α10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in rodent OHCs, we report that these two Ca2+ entry sites are closely positioned, but present different regulation mechanisms. Ca2+ spread from MOC synapses is contained by cisternal Ca2+-ATPases. Considered a weak drive for transmitter release, we unexpectedly found that VGCC Ca2+ signals are comparable in size to those elicited by α9α10 and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca2+ control function in cardiomy-ocytes, regulates basal Ca2+ levels and MOC synaptic activity in OHCs.

scholarly journals Overexpression of SK2 Channels Enhances Efferent Suppression of Cochlear Responses Without Enhancing Noise Resistance

2007 ◽  
Vol 97 (4) ◽  
pp. 2930-2936 ◽  
Author(s):  
Stéphane F. Maison ◽  
Lisan L. Parker ◽  
Lucy Young ◽  
John P. Adelman ◽  
Jian Zuo ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Hair Cells ◽  
Otoacoustic Emissions ◽  
Outer Hair Cell ◽  
Outer Hair Cells ◽  
Sk Channels ◽  
Cochlear Function ◽  
Cochlear Hair Cells ◽  
Efferent Suppression

Cochlear hair cells express SK2, a small-conductance Ca2+-activated K+ channel thought to act in concert with Ca2+-permeable nicotinic acetylcholine receptors (nAChRs) α9 and α10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the α9/α10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in α9 overexpresser mice; however, in contrast to α9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca2+ entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility.

Spontaneous reversibility of damage to outer hair cells after sodium salicylate induced ototoxicity

2011 ◽  
Vol 125 (8) ◽  
pp. 786-794 ◽  
Author(s):  
I de Almeida-Silva ◽  
J A A de Oliveira ◽  
M Rossato ◽  
F Fiacadori Salata ◽  
M A Hyppolito
Keyword(s):  
Hair Cell ◽  
Drug Administration ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Sodium Salicylate ◽  
Cell Structure ◽  
Outer Hair Cells ◽  
Cochlear Function ◽  
Action Function ◽  
High Sodium

AbstractBackground:High sodium salicylate doses can cause reversible hearing loss and tinnitus, possibly due to reduced outer hair cell electromotility. Sodium salicylate is known to alter outer hair cell structure and function. This study determined the reversibility and cochlear recovery time after administration of an ototoxic sodium salicylate dose to guinea pigs with normal cochlear function.Study design:Prospective experimental investigation.Methods:All animals received a single 500 mg sodium salicylate dose, but with different durations of action. Function was evaluated before drug administration and immediately before sacrifice. Cochleae were processed and viewed using scanning electron microscopy.Results:Changes in outer hair cell function were observed to be present 2 hours after drug administration, with recovery of normal anatomy beginning after 24 hours. Subsequently, derangement and distortion of cilia reduced, with effects predominantly in row three. At 168 hours, cilia were near-normal but with mild distortions which interfered with normal cochlear physiology.Conclusions:Ciliary changes persisted for up to 168 hours after ototoxic sodium salicylate administration.

scholarly journals The frequency limit of outer hair cell motility measured in vivo

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Anna Vavakou ◽  
Nigel P Cooper ◽  
Marcel van der Heijden
Keyword(s):  
Outer Hair Cell ◽  
Gain Control ◽  
Outer Hair Cells ◽  
Corner Frequency ◽  
Cochlear Function ◽  
Cycle Basis ◽  
Low Pass ◽  
Cochlear Hearing Loss ◽  
Length Changes

Outer hair cells (OHCs) in the mammalian ear exhibit electromotility, electrically driven somatic length changes that are thought to mechanically amplify sound-evoked vibrations. For this amplification to work, OHCs must respond to sounds on a cycle-by-cycle basis even at frequencies that exceed the low-pass corner frequency of their cell membranes. Using in vivo optical vibrometry we tested this theory by measuring sound-evoked motility in the 13–25 kHz region of the gerbil cochlea. OHC vibrations were strongly rectified, and motility exhibited first-order low-pass characteristics with corner frequencies around 3 kHz– more than 2.5 octaves below the frequencies the OHCs are expected to amplify. These observations lead us to suggest that the OHCs operate more like the envelope detectors in a classical gain-control scheme than like high-frequency sound amplifiers. These findings call for a fundamental reconsideration of the role of the OHCs in cochlear function and the causes of cochlear hearing loss.

Modeling the Mechanics of Tethers Pulled From the Cochlear Outer Hair Cell Membrane

2008 ◽  
Vol 130 (3) ◽  
Author(s):  
Kristopher R. Schumacher ◽  
Aleksander S. Popel ◽  
Bahman Anvari ◽  
William E. Brownell ◽  
Alexander A. Spector
Keyword(s):  
Cell Membrane ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Lateral Wall ◽  
Outer Hair Cells ◽  
The Body ◽  
Computational Method ◽  
Membrane Properties ◽  
Bending Modulus ◽  
Sound Amplification

Cell membrane tethers are formed naturally (e.g., in leukocyte rolling) and experimentally to probe membrane properties. In cochlear outer hair cells, the plasma membrane is part of the trilayer lateral wall, where the membrane is attached to the cytoskeleton by a system of radial pillars. The mechanics of these cells is important to the sound amplification and frequency selectivity of the ear. We present a modeling study to simulate the membrane deflection, bending, and interaction with the cytoskeleton in the outer hair cell tether pulling experiment. In our analysis, three regions of the membrane are considered: the body of a cylindrical tether, the area where the membrane is attached and interacts with the cytoskeleton, and the transition region between the two. By using a computational method, we found the shape of the membrane in all three regions over a range of tether lengths and forces observed in experiments. We also analyze the effects of biophysical properties of the membrane, including the bending modulus and the forces of the membrane adhesion to the cytoskeleton. The model’s results provide a better understanding of the mechanics of tethers pulled from cell membranes.

scholarly journals Sex-related effects on diabetes-induced alterations in calcium release in the rat heart

2007 ◽  
Vol 293 (6) ◽  
pp. H3584-H3592 ◽  
Author(s):  
Nazmi Yaras ◽  
Erkan Tuncay ◽  
Nuhan Purali ◽  
Babur Sahinoglu ◽  
Guy Vassort ◽  
...  
Keyword(s):  
Calcium Release ◽  
Binding Protein ◽  
Ryanodine Receptors ◽  
Left Ventricular ◽  
Adult Rats ◽  
Fk506 Binding Protein ◽  
Pressure Development ◽  
Spatiotemporal Parameters ◽  
Intracellular Ca ◽  
Developed Pressure

The present study was designed to determine whether the properties of local Ca2+ release and its related regulatory mechanisms might provide insight into the role of sex differences in heart functions of control and streptozotocin-induced diabetic adult rats. Left ventricular developed pressure, the rates of pressure development and decay (±dP/d t), basal intracellular Ca2+ level ([Ca2+]i), and spatiotemporal parameters of [Ca2+]i transients were found to be similar in male and female control rats. However, spatiotemporal parameters of Ca2+ sparks in cardiomyocytes isolated from control females were significantly larger and slower than those in control males. Diabetes reduced left ventricular developed pressure to a lower extent in females than in males, and the diabetes-induced depressions in both +dP/d t and −dP/d t were less in females than in males. Diabetes elicited a smaller reduction in the amplitude of [Ca2+]i transients in females than in males, a smaller reduction in sarcoplasmic reticulum-Ca2+ load, and less increase in basal [Ca2+]i. Similarly, the elementary Ca2+ events and their control proteins were clearly different in both sexes, and these differences were more marked in diabetes. Diabetes-induced depression of the Ca2+ spark amplitude was significantly less in females than in matched males. Levels of cardiac ryanodine receptors (RyR2) and FK506-binding protein 12.6 in control females were significantly higher than those shown in control males. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and free sulfhydryl groups were significantly less reduced, and PKC levels were less increased, in diabetic females than in diabetic males. The present data related to local Ca2+ release and its related proteins describe some of the mechanisms that may underlie sex-related differences accounting for females to have less frequent development of cardiac diseases.

Innate immune response in CF airway epithelia: hyperinflammatory?

2006 ◽  
Vol 291 (2) ◽  
pp. C218-C230 ◽  
Author(s):  
Terry E. Machen
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Cellular Signaling ◽  
Basolateral Membrane ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Intracellular Ca

The lack of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the apical membranes of CF airway epithelial cells abolishes cAMP-stimulated anion transport, and bacteria, eventually including Pseudomonas aeruginosa, bind to and accumulate in the mucus. Flagellin released from P. aeruginosa triggers airway epithelial Toll-like receptor 5 and subsequent NF-κB signaling and production and release of proinflammatory cytokines that recruit neutrophils to the infected region. This response has been termed hyperinflammatory because so many neutrophils accumulate; a response that damages CF lung tissue. We first review the contradictory data both for and against the idea that epithelial cells exhibit larger-than-normal proinflammatory signaling in CF compared with non-CF cells and then review proposals that might explain how reduced CFTR function could activate such proinflammatory signaling. It is concluded that apparent exaggerated innate immune response of CF airway epithelial cells may have resulted not from direct effects of CFTR on cellular signaling or inflammatory mediator production but from indirect effects resulting from the absence of CFTRs apical membrane channel function. Thus, loss of Cl−, HCO3−, and glutathione secretion may lead to reduced volume and increased acidification and oxidation of the airway surface liquid. These changes concentrate proinflammatory mediators, reduce mucociliary clearance of bacteria and subsequently activate cellular signaling. Loss of apical CFTR will also hyperpolarize basolateral membrane potentials, potentially leading to increases in cytosolic [Ca2+], intracellular Ca2+, and NF-κB signaling. This hyperinflammatory effect of CF on intracellular Ca2+and NF-κB signaling would be most prominently expressed during exposure to both P. aeruginosa and also endocrine, paracrine, or nervous agonists that activate Ca2+signaling in the airway epithelia.

scholarly journals Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum.

1994 ◽  
Vol 5 (1) ◽  
pp. 97-103 ◽  
Author(s):  
I Bezprozvanny ◽  
S Bezprozvannaya ◽  
B E Ehrlich
Keyword(s):  
Lipid Bilayers ◽  
Inhibitory Action ◽  
Single Channel ◽  
Ryanodine Receptors ◽  
Single Channels ◽  
Ca Channels ◽  
Open Time ◽  
Inositol 1,4,5 Trisphosphate ◽  
Insp3 Receptors ◽  
Intracellular Ca

Effects of the xanthine drug caffeine on inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels from canine cerebellum were studied using single channels incorporated into planar lipid bilayers. Caffeine, used widely as an agonist of ryanodine receptors, inhibited the activity of InsP3-gated Ca channels in a noncooperative fashion with half-inhibition at 1.64 mM caffeine. The frequency of channel openings was decreased more than threefold after addition of 5 mM caffeine; there was only a small effect on mean open time of the channels, and the single channel conductance was unchanged. Increased InsP3 concentration overcame the inhibitory action of caffeine, but caffeine did not reduce specific [3H]InsP3 binding to the receptor. The inhibitory action of caffeine on InsP3 receptors suggests that the action of caffeine on the intracellular Ca pool must be interpreted with caution when both ryanodine receptors and InsP3 receptors are present in the cell.

The location and mechanism of electromotility in guinea pig outer hair cells

1993 ◽  
Vol 70 (2) ◽  
pp. 549-558 ◽  
Author(s):  
R. Hallworth ◽  
B. N. Evans ◽  
P. Dallos
Keyword(s):  
Guinea Pig ◽  
Hair Cells ◽  
Outer Hair Cell ◽  
Length Change ◽  
Opposite Polarity ◽  
Outer Hair Cells ◽  
Response Amplitude ◽  
Change Function ◽  
Length Changes ◽  
Diameter Change

1. The microchamber method was used to examine the motile responses of isolated guinea pig outer hair cells to electrical stimulation. In the microchamber method, an isolated cell is drawn partway into a suction pipette and stimulated transcellularly. The relative position of the cell in the microchamber is referred to as the exclusion fraction. 2. The length changes of the included and excluded segments were compared for constant sinusoidal stimulus amplitude as functions of the exclusion fraction. Both included and excluded segments showed maximal responses when the cell was excluded approximately halfway. Both segments showed smaller or absent responses when the cell was almost fully excluded or almost fully included. 3. When the cell was near to, but not at, the maximum exclusion, the included segment response amplitude was zero, whereas the excluded segment response amplitude was nonzero. In contrast, when the cell was nearly fully included, the excluded segment response amplitude was zero, but the included segment response amplitude was still detectable. A simple model of outer hair cell motility based on these results suggests that the cell has finite-resistance terminations and that the motors are restricted to a region above the nucleus and below its ciliated apex (cuticular plate). 4. The function describing length change as a function of command voltage was measured for each segment as the exclusion fraction was varied. The functions were similar at midrange exclusions (i.e., when the segments were about equal length), showing nonlinearity and saturability. The functions were strikingly different when the segment lengths were different. The effects of exclusion on the voltage to length-change functions suggested that the nonlinearity and saturability are local properties of the motility mechanism. 5. The diameter changes of both segments were examined. The segment diameter changes were always antiphasic to the length changes. This finding implies that the motility mechanism has an active antiphasic diameter component. The diameter change amplitude was a monotonically increasing function of exclusion for the included segment, and a decreasing function for the excluded segment. 6. The voltage to length-change and voltage to diameter-change functions were measured for the same cell and exclusion fraction. The voltage to diameter-change function was smaller in amplitude than the voltage to length-change function. The functions were of opposite polarity to each other, but were otherwise similar in character. Thus it is likely that the same motor mechanism is responsible for both axial and diameter deformations.

scholarly journals Dust from hog confinement facilities impairs Ca2+ mobilization from sarco(endo)plasmic reticulum by inhibiting ryanodine receptors

2013 ◽  
Vol 114 (5) ◽  
pp. 665-674
Author(s):  
Chengju Tian ◽  
Caronda J. Moore ◽  
Puttappa Dodmane ◽  
Chun Hong Shao ◽  
Debra J. Romberger ◽  
...  
Keyword(s):  
Binding Sites ◽  
Molecular Mechanisms ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
C2c12 Cells ◽  
Common Element ◽  
Plasmic Reticulum ◽  
Skeletal Muscle Weakness ◽  
Intracellular Ca ◽  
Phosphate Buffered Saline

Individuals working in commercial hog confinement facilities have elevated incidences of headaches, depression, nausea, skeletal muscle weakness, fatigue, gastrointestinal disorders, and cardiovascular diseases, and the molecular mechanisms for these nonrespiratory ailments remain incompletely undefined. A common element underlying these diverse pathophysiologies is perturbation of intracellular Ca2+ homeostasis. This study assessed whether the dust generated inside hog confinement facilities contains compounds that alter Ca2+ mobilization via ryanodine receptors (RyRs), key intracellular channels responsible for mobilizing Ca2+ from internal stores to elicit an array of physiologic functions. Hog barn dust (HBD) was extracted with phosphate-buffered saline, sterile-filtered (0.22 μm), and size-separated using Sephadex G-100 resin. Fractions (F) 1 through 9 (Mw >10,000 Da) had no measurable effects on RyR isoforms. However, F10 through F17, which contained compounds of Mw ≤2,000 Da, modulated the [3H]ryanodine binding to RyR1, RyR2, and RyR3 in a biphasic (Gaussian) manner. The Ki values for F13, the most potent fraction, were 3.8 ± 0.2 μg/ml for RyR1, 0.2 ± 0.01 μg/ml and 19.1 ± 2.8 μg/ml for RyR2 (two binding sites), and 44.9 ± 2.8 μg/ml and 501.6 ± 9.2 μg/ml for RyR3 (two binding sites). In lipid bilayer assays, F13 dose-dependently decreased the open probabilities of RyR1, RyR2, and RyR3. Pretreating differentiated mouse skeletal myotubes (C2C12 cells) with F13 blunted the amplitudes of ryanodine- and K+-induced Ca2+ transients. Because RyRs are present in many cell types, impairment in Ca2+ mobilization from internal stores via these channels is a possible mechanism by which HBD may trigger these seemingly unrelated pathophysiologies.

Characterization of postsynaptic Ca2+ signals at the Drosophila larval NMJ

2011 ◽  
Vol 106 (2) ◽  
pp. 710-721 ◽  
Author(s):  
Sunil A. Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Efficacy ◽  
Single Action ◽  
Synaptic Homeostasis ◽  
Multiple Transcripts ◽  
Quantal Size ◽  
Intracellular Ca ◽  
Larval Neuromuscular Junction

Postsynaptic intracellular Ca2+ concentration ([Ca2+]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca2+ signals can alter synaptic efficacy by influencing transmitter release, receptor sensitivity, and protein synthesis. We examined the postsynaptic Ca2+ transients at the Drosophila larval neuromuscular junction (NMJ) by injecting the muscle fibers with Ca2+ indicators rhod-2 and Oregon Green BAPTA-1 (OGB-1) and then monitoring their increased fluorescence during synaptic activity. We observed discrete postsynaptic Ca2+ transients along the NMJ during single action potentials (APs) and quantal Ca2+ transients produced by spontaneous transmitter release. Most of the evoked Ca2+ transients resulted from the release of one or two quanta of transmitter and occurred largely at synaptic boutons. The magnitude of the Ca2+ signals was correlated with synaptic efficacy; the Is terminals, which produce larger excitatory postsynaptic potentials (EPSPs) and have a greater quantal size than Ib terminals, produced a larger Ca2+ signal per terminal length and larger quantal Ca2+ signals than the Ib terminals. During a train of APs, the postsynaptic Ca2+ signal increased but remained localized to the postsynaptic membrane. In addition, we showed that the plasma membrane Ca2+-ATPase (PMCA) played a role in extruding Ca2+ from the postsynaptic region of the muscle. Drosophila melanogaster has a single PMCA gene, predicted to give rise to various isoforms by alternative splicing. Using RT-PCR, we detected the expression of multiple transcripts in muscle and nervous tissues; the physiological significance of the same is yet to be determined.

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