Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Assoc Res Otolaryngol
2007 Dec 01;84:474-83. doi: 10.1177/026119290703500302.
Show Gene links
Show Anatomy links
Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells.
Zorrilla de San Martín J, Ballestero J, Katz E, Elgoyhen AB, Fuchs PA.
???displayArticle.abstract???
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 'ryanodine 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 alpha9alpha10-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 alpha9alpha10 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 microM 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 'short' hair cells likewise was enhanced in the presence of 100 microM ryanodine. This facilitatory effect on current through the AChR could enhance brief ( approximately 1 s) activation of associated calcium-dependent 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 alpha9alpha10-mediated responses and for potential inner ear therapeutics based on this interaction.
Blanchet,
Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors.
1996, Pubmed
Blanchet,
Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors.
1996,
Pubmed Boton,
Two calcium-activated chloride conductances in Xenopus laevis oocytes permeabilized with the ionophore A23187.
1989,
Pubmed
,
Xenbase Buck,
Ryanodine stabilizes multiple conformational states of the skeletal muscle calcium release channel.
1992,
Pubmed Conroy,
Potentiation of alpha7-containing nicotinic acetylcholine receptors by select albumins.
2003,
Pubmed Coronado,
Structure and function of ryanodine receptors.
1994,
Pubmed Curtis,
Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol.
2002,
Pubmed
,
Xenbase Elgoyhen,
Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.
1994,
Pubmed
,
Xenbase Elgoyhen,
alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells.
2001,
Pubmed
,
Xenbase Evans,
Acetylcholine activates two currents in guinea-pig outer hair cells.
1996,
Pubmed Eybalin,
Neurotransmitters and neuromodulators of the mammalian cochlea.
1993,
Pubmed Fuchs,
A novel cholinergic receptor mediates inhibition of chick cochlear hair cells.
1992,
Pubmed Fuchs,
Cholinergic inhibition of short (outer) hair cells of the chick's cochlea.
1992,
Pubmed Glowatzki,
Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.
2000,
Pubmed Gómez-Casati,
Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells.
2005,
Pubmed Harris,
Effects of nicotine on cognitive deficits in schizophrenia.
2004,
Pubmed Hogg,
Nicotinic acetylcholine receptors as drug targets.
2004,
Pubmed Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase Katz,
Developmental regulation of nicotinic synapses on cochlear inner hair cells.
2004,
Pubmed Katz,
High calcium permeability and calcium block of the alpha9 nicotinic acetylcholine receptor.
2000,
Pubmed
,
Xenbase Krause,
Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor.
1998,
Pubmed
,
Xenbase Lilly,
Ryanodine-induced calcium release from hepatic microsomes and permeabilized hepatocytes.
1995,
Pubmed Lioudyno,
A "synaptoplasmic cistern" mediates rapid inhibition of cochlear hair cells.
2004,
Pubmed Lustig,
Molecular cloning and mapping of the human nicotinic acetylcholine receptor alpha10 (CHRNA10).
2001,
Pubmed Macdonald,
GABAA receptor channels.
1994,
Pubmed Nenov,
Acetylcholine response in guinea pig outer hair cells. II. Activation of a small conductance Ca(2+)-activated K+ channel.
1996,
Pubmed Oliver,
Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic transmission at auditory outer hair cells.
2000,
Pubmed Parys,
Isolation, characterization, and localization of the inositol 1,4,5-trisphosphate receptor protein in Xenopus laevis oocytes.
1992,
Pubmed
,
Xenbase Rothlin,
The alpha9 nicotinic acetylcholine receptor shares pharmacological properties with type A gamma-aminobutyric acid, glycine, and type 3 serotonin receptors.
1999,
Pubmed
,
Xenbase Rousseau,
Ryanodine modifies conductance and gating behavior of single Ca2+ release channel.
1987,
Pubmed Saito,
Fine structure of the sensory epithelium of guinea-pig organ of Corti: subsurface cisternae and lamellar bodies in the outer hair cells.
1983,
Pubmed Sgard,
A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit.
2002,
Pubmed
,
Xenbase Smith,
Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia.
2002,
Pubmed Sridhar,
Unique postsynaptic signaling at the hair cell efferent synapse permits calcium to evoke changes on two time scales.
1997,
Pubmed Sutko,
The pharmacology of ryanodine and related compounds.
1997,
Pubmed Zwart,
5-Hydroxyindole potentiates human alpha 7 nicotinic receptor-mediated responses and enhances acetylcholine-induced glutamate release in cerebellar slices.
2002,
Pubmed
,
Xenbase
