A “Synaptoplasmic Cistern” Mediates Rapid Inhibition of Cochlear Hair Cells

Lioudyno, Maria; Hiel, Hakim; Kong, Jee Hyun; Katz, Eleonora; Waldman, Erik H.; Parameshwaran-Iyer, Suchitra; Glowatzki, Elisabeth; Fuchs, Paul

doi:10.1523/jneurosci.3674-04.2004

Cited by 109 publications

(141 citation statements)

References 38 publications

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“…More significantly, these are at odds with earlier work showing that ryanodine inhibits cholinergic action on outer hair cells of the rat cochlea (Lioudyno et al 2004). In the present study, high concentrations of ryanodine (100 mM) prolonged the SK current generated in rat OHCs by a brief application of ACh (Fig.…”

Section: Comparisons To Earlier Workcontrasting

confidence: 99%

“…Ryanodine is a plant alkaloid that affects calciumrelease channels, Fryanodine receptors_ (RyR) present in internal calcium stores identified in a variety of cell systems (Coronado et al 1994;Rousseau et al 1987) including hair cells of the cochlea (Lioudyno et al 2004). Although an agonist at low concentrations, ryanodine acts as an antagonist of the calciumrelease channels at higher concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the postsynaptic hair cell is endowed with a synaptic cistern coextensive with the presynaptic efferent contacts (Saito 1983). The term Bsynaptoplasmicĉ istern of the hair cell was coined to recognize an analogy to the sarcoplasmic reticulum of muscle (Lioudyno et al 2004). It has recently been shown that calcium-activated potassium currents in rat outer hair cells evoked by ACh were altered by compounds that act on intracellular calcium stores, presumably the closely associated synaptoplasmic cistern.…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been shown that calcium-activated potassium currents in rat outer hair cells evoked by ACh were altered by compounds that act on intracellular calcium stores, presumably the closely associated synaptoplasmic cistern. Calcium-induced calcium release by RyRs has been proposed as the most likely mechanism of store coupling in hair cells of the cochlea (Lioudyno et al 2004). Thus, as in muscle, where tight coupling of voltage-gated calcium channels to ryanodine receptors in the sarcoplasmic reticulum mediates calcium-induced calcium release, nAChRs trigger a subsequent calcium-dependent process in hair cells.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, nicotine and most nicotinic agonists, except for ACh, behave as antagonists, or very weak partial agonists, of this receptor subtype. Given that the a9a10-containing hair cell cholinergic receptor is sensitive to a wide variety of chemically different compounds and that store coupling through calcium-induced calciumrelease in hair cells has been proposed on the basis of pharmacological approaches (Lioudyno et al 2004), we examined the direct action of ryanodine on a9a10-containing nAChRs. We report that ryanodine, in addition to acting on cytoplasmic calcium stores, is a positive modulator of the hair cell nAChR, the first such compound to be found.…”

Section: Introductionmentioning

confidence: 99%

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Ryanodine is a Positive Modulator of Acetylcholine Receptor Gating in Cochlear Hair Cells

Martín

Ballestero

Katz

et al. 2007

JARO

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The efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern, whose presence suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores include Fryanodine receptors_, whose participation is usually demonstrated by sensitivity to the eponymous plant alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells could be confounded by the unusual pharmacology of the a9a10-containing hair cell nicotinic cholinergic receptor (nAChR), which has been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine, rather than antagonizing, is a positive modulator of the a9a10 nAChR expressed in Xenopus oocytes, the first such compound to be found. The effect of ryanodine was to increase the apparent affinity and efficacy for acetylcholine (ACh). Correspondingly, ACh-evoked currents through the isolated cholinergic receptors of inner hair cells in excised mouse cochleas were approximately doubled by 200 mM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This unusual positive modulation was not unique to the mammalian receptor. The response to ACh of chicken Fshort_ hair cells likewise was enhanced in the presence of 100 mM ryanodine. This facilitatory effect on current through the AChR could enhance brief (õ1 s) activation of associated calciumdependent K + (SK) channels in both chicken short hair cells and rat outer hair cells. This novel effect of ryanodine provides new opportunities for the design of compounds that potentiate a9a10-mediated responses and for potential inner ear therapeutics based on this interaction.

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Section: Comparisons To Earlier Workcontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ryanodine is a Positive Modulator of Acetylcholine Receptor Gating in Cochlear Hair Cells

Martín

Ballestero

Katz

et al. 2007

JARO

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Nicotinic acetylcholine receptor structure and function in the efferent auditory system

Lustig

2006

Anat. Rec.

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This article reviews and presents new data regarding the nicotinic acetylcholine receptor subunits ␣9 and ␣10. Although phylogentically ancient, these subunits have only recently been identified as critical components of the efferent auditory system and medial olivocochlear pathway. This pathway is important in auditory processing by modulating outer hair cell function to broadly tune the cochlea and improve signal detection in noise. Pharmacologic properties of the functionally expressed ␣9␣10 receptor closely resemble the cholinergic response of outer hair cells. Molecular, immunohistochemical, and knockout mice studies have added further weight to the role this receptor plays in mediating the efferent auditory response. Alternate and complementary mechanisms of outer hair cell efferent activity might also be mediated through the nAChR ␣9␣10, either through secondary calcium stores, second messengers, or direct proteinprotein interactions. We investigated protein-protein interactions using a yeast-two-hybrid screen of the nAChR ␣10 intracellular loop against a rat cochlear cDNA library. Among the identified proteins was prosaposin, a precursor of saposins, which have been shown to act as neurotrophic factors in culture, can bind to a putative G0-coupled cell surface receptor, and may be involved in the prevention of cell death. This study and review suggest that nAChR ␣9␣10 may represent a potential therapeutic target for a variety of ear disorders, including preventing or treating noise-induced hearing loss, or such debilitating disorders as vertigo or tinnitus. Anat Rec Part 288A: 424 -434, 2006.

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Ultrastructure of cisternal synapses on outer hair cells of the mouse cochlea

Fuchs

Lehar

Hiel

2013

J of Comparative Neurology

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C (cisternal) synapses with a near membrane postsynaptic cistern are found on motor neurons and other central neurons, where their functional role is unknown. Similarly structured cisternal synapses mediate cholinergic inhibition of cochlear hair cells via α9α10-containing ionotropic receptors and associated calcium-activated (SK2) potassium channels, providing the opportunity to examine the ultrastructure of genetically altered cisternal synapses. Serial section electron microscopy was used to examine efferent synapses of outer hair cells (OHCs) in mice with diminished or enhanced cholinergic inhibition. The contact area of efferent terminals, the appositional area of the postsynaptic cistern, the distance of the cistern from the plasma membrane, and the average width of the cisternal lumen were recorded. The synaptic cisterns of wild- type OHCs were closely aligned (14-nm separation) with the hair cell membrane and coextensive with the micrometers-long synaptic terminals. The cisternal lumen averaged 18 nm so that the cisternal volume was approximately 30% larger than that of the cytoplasmic space between the cistern and the plasma membrane. Synaptic ultrastructure of α9L9′T knockin OHCs (acetylcholine receptor gain of function) were like those of wild-type littermates except that cisternal volumes were significantly larger. OHCs of SK2 knockout mice had few small efferent terminals. Synaptic cisterns were present, but smaller than those of wild-type littermates. Taken together, these data suggest that the cistern serves as a sink or buffer to isolate synaptic calcium signals. J. Comp. Neurol. 522:717-729, 2014.

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A “Synaptoplasmic Cistern” Mediates Rapid Inhibition of Cochlear Hair Cells

Cited by 109 publications

References 38 publications

Ryanodine is a Positive Modulator of Acetylcholine Receptor Gating in Cochlear Hair Cells

Ryanodine is a Positive Modulator of Acetylcholine Receptor Gating in Cochlear Hair Cells

Nicotinic acetylcholine receptor structure and function in the efferent auditory system

Ultrastructure of cisternal synapses on outer hair cells of the mouse cochlea

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