The Function and Molecular Identify of Inward Rectifier Channels in Vestibular Hair Cells of the Mouse Inner Ear

2012 ◽  
Author(s):  
Michaela E. Levin
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Inward Rectifier ◽  
Vestibular Hair Cells ◽  
Inward Rectifier Channels

scholarly journals The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

2012 ◽  
Vol 108 (1) ◽  
pp. 175-186 ◽  
Author(s):  
Michaela E. Levin ◽  
Jeffrey R. Holt
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Inward Rectifier ◽  
Molecular Composition ◽  
Equilibrium Potential ◽  
Type Ii ◽  
Wild Type ◽  
Vestibular Hair Cells ◽  
Molecular Identity ◽  
Voltage Dependent

Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS ( n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/−mice had significantly ( P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections.

Ionic Currents and Electromotility in Inner Ear Hair Cells From Humans

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Ionic Currents ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Sensory Receptor ◽  
Surgical Removal ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Sensory Receptor Cells

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

scholarly journals Celsr1 coordinates the planar polarity of vestibular hair cells during inner ear development

2017 ◽  
Vol 423 (2) ◽  
pp. 126-137 ◽  
Author(s):  
Jeremy S. Duncan ◽  
Michelle L. Stoller ◽  
Andrew F. Francl ◽  
Fadel Tissir ◽  
Danelle Devenport ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Planar Polarity ◽  
Ear Development ◽  
Vestibular Hair Cells ◽  
Inner Ear Development

Channeling your inner ear potassium: K+ channels in vestibular hair cells

2016 ◽  
Vol 338 ◽  
pp. 40-51 ◽  
Author(s):  
Frances L. Meredith ◽  
Katherine J. Rennie
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
K Channels ◽  
Vestibular Hair Cells

scholarly journals Conserved and Divergent Principles of Planar Polarity Revealed by Hair Cell Development and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Michael R. Deans
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Model Organism ◽  
Vestibular Function ◽  
Sensory Receptor ◽  
Apical Surface ◽  
Planar Polarity ◽  
Vestibular Hair Cells ◽  
Sensory Epithelia

Planar polarity describes the organization and orientation of polarized cells or cellular structures within the plane of an epithelium. The sensory receptor hair cells of the vertebrate inner ear have been recognized as a preeminent vertebrate model system for studying planar polarity and its development. This is principally because planar polarity in the inner ear is structurally and molecularly apparent and therefore easy to visualize. Inner ear planar polarity is also functionally significant because hair cells are mechanosensors stimulated by sound or motion and planar polarity underlies the mechanosensory mechanism, thereby facilitating the auditory and vestibular functions of the ear. Structurally, hair cell planar polarity is evident in the organization of a polarized bundle of actin-based protrusions from the apical surface called stereocilia that is necessary for mechanosensation and when stereociliary bundle is disrupted auditory and vestibular behavioral deficits emerge. Hair cells are distributed between six sensory epithelia within the inner ear that have evolved unique patterns of planar polarity that facilitate auditory or vestibular function. Thus, specialized adaptations of planar polarity have occurred that distinguish auditory and vestibular hair cells and will be described throughout this review. There are also three levels of planar polarity organization that can be visualized within the vertebrate inner ear. These are the intrinsic polarity of individual hair cells, the planar cell polarity or coordinated orientation of cells within the epithelia, and planar bipolarity; an organization unique to a subset of vestibular hair cells in which the stereociliary bundles are oriented in opposite directions but remain aligned along a common polarity axis. The inner ear with its complement of auditory and vestibular sensory epithelia allows these levels, and the inter-relationships between them, to be studied using a single model organism. The purpose of this review is to introduce the functional significance of planar polarity in the auditory and vestibular systems and our contemporary understanding of the developmental mechanisms associated with organizing planar polarity at these three cellular levels.

scholarly journals Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells

2021 ◽  
Author(s):  
Francesco Gianoli ◽  
Brenna Hogan ◽  
&Eacutemilien Dilly ◽  
Thomas Risler ◽  
Andrei S Kozlov
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Current Model ◽  
Low Frequency ◽  
Reaction Rates ◽  
Hopf Bifurcations ◽  
Active Process ◽  
Auditory Hair Cells ◽  
Cycle Basis ◽  
Vestibular Hair Cells

Since the pioneering work of Thomas Gold published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Termed the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear's mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive—especially at the high frequencies characteristic of mammalian hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has previously been proposed that a cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here, we ground our study on our previous model of hair-cell mechanotransduction, which relied on the cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, our model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. In contrast to the myosin-based mechanism, responsible for low-frequency relaxation oscillations in the vestibular hair cells of amphibians, the current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the single mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of mammalian hearing.

scholarly journals Molecular Identity and Functional Properties of a Novel T-Type Ca2+ Channel Cloned From the Sensory Epithelia of the Mouse Inner Ear

2008 ◽  
Vol 100 (4) ◽  
pp. 2287-2299 ◽  
Author(s):  
Liping Nie ◽  
Jun Zhu ◽  
Michael Anne Gratton ◽  
Amy Liao ◽  
Karen J. Mu ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Synapse Formation ◽  
Divalent Cations ◽  
Functional Expression ◽  
Basilar Papilla ◽  
Vestibular Hair Cells ◽  
Molecular Identity ◽  
Sensory Epithelia ◽  
Permeation Properties

The molecular identity of non-Cav1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca2+-dependent functions is indisputable. Recently, a transient Cav3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Cav3.1 current promotes spontaneous activity of the developing hair cell, which may be essential for synapse formation. Here, we have isolated and sequenced the full-length complementary DNA of a distinct isoform of Cav3.1 in the mouse inner ear. The channel is derived from alternative splicing of exon14, exon25A, exon34, and exon35. Functional expression of the channel in Xenopus oocytes yielded Ca2+ currents, which have a permeation phenotype consistent with T-type channels. However, unlike most multiion channels, the T-type channel does not exhibit the anomalous mole fraction effect, possibly reflecting comparable permeation properties of divalent cations. The Cav3.1 channel was expressed in sensory and nonsensory epithelia of the inner ear. Moreover, there are profound changes in the expression levels during development. The differential expression of the channel during development and the pharmacology of the inner ear Cav3.1 channel may have contributed to the difficulties associated with identification of the non-Cav1.3 currents.

scholarly journals Differentiation of embryonic stem cells into inner ear vestibular hair cells using vestibular cell derived-conditioned medium

2019 ◽  
Vol 19 ◽  
pp. 100649
Author(s):  
Masaharu Sakagami ◽  
Yukiteru Ouji ◽  
Norikazu Kawai ◽  
Masayasu Misu ◽  
Masahide Yoshikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Inner Ear ◽  
Conditioned Medium ◽  
Hair Cells ◽  
Embryonic Stem ◽  
Vestibular Hair Cells

scholarly journals The lhfpl5 ohnologs lhfpl5a and lhfpl5b are required for mechanotransduction in distinct populations of sensory hair cells in zebrafish

2019 ◽  
Author(s):  
Timothy Erickson ◽  
Itallia V. Pacentine ◽  
Alexandra Venuto ◽  
Rachel Clemens ◽  
Teresa Nicolson
Keyword(s):  
Inner Ear ◽  
Lateral Line ◽  
Hair Cells ◽  
Vestibular Function ◽  
Fusion Partner ◽  
Primary Role ◽  
Mechanical Stimuli ◽  
Vestibular Hair Cells ◽  
Lateral Line Organ ◽  
Line Organ

1AbstractHair cells sense and transmit auditory, vestibular, and hydrodynamic information by converting mechanical stimuli into electrical signals. This process of mechano-electrical transduction (MET) requires a mechanically-gated channel localized in the apical stereocilia of hair cells. In mice, lipoma HMGIC fusion partner-like 5 (LHFPL5) acts as an auxiliary subunit of the MET channel whose primary role is to correctly localize PCDH15 and TMC1 to the mechanotransduction complex. Zebrafish have two lhfpl5 genes (lhfpl5a and lhfpl5b), but their individual contributions to MET channel assembly and function have not been analyzed.Here we show that the zebrafish lhfpl5 genes are expressed in discrete populations of hair cells: lhfpl5a expression is restricted to auditory and vestibular hair cells in the inner ear, while lhfpl5b expression is specific to hair cells of the lateral line organ. Consequently, lhfpl5a mutants exhibit defects in auditory and vestibular function, while disruption of lhfpl5b affects hair cells only in the lateral line neuromasts. In contrast to previous reports in mice, localization of Tmc1 does not depend upon Lhfpl5 function in either the inner ear or lateral line organ. In both lhfpl5a and lhfpl5b mutants, GFP-tagged Tmc1 and Tmc2b proteins still localize to the stereocilia of hair cells. Using a stably integrated GFP-Lhfpl5a transgene, we show that the tip link cadherins Pcdh15a and Cdh23, along with the Myo7aa motor protein, are required for correct Lhfpl5a localization at the tips of stereocilia. Our work corroborates the evolutionarily conserved co-dependence between Lhfpl5 and Pcdh15, but also reveals novel requirements for Cdh23 and Myo7aa to correctly localize Lhfpl5a. In addition, our data suggest that targeting of Tmc1 and Tmc2b proteins to stereocilia in zebrafish hair cells occurs independently of Lhfpl5 proteins.

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