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J Assoc Res Otolaryngol
2004 Sep 01;53:261-9. doi: 10.1007/s10162-004-4025-6.
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Linopirdine blocks alpha9alpha10-containing nicotinic cholinergic receptors of cochlear hair cells.
Gomez-Casati ME
,
Katz E
,
Glowatzki E
,
Lioudyno MI
,
Fuchs P
,
Elgoyhen AB
.
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Studies of the electrophysiological response to acetylcholine (ACh) in mammalian outer hair cells (OHCs) are hindered by the presence of a large potassium current, I(K,n), most likely mediated by channels containing the KCNQ4 subunit. Since I(K,n) can be blocked by linopirdine, cholinergic effects might be better revealed in the presence of this compound. The aim of the present work was to study the effects of linopirdine on the ACh-evoked responses through alpha9alpha10-containing native and recombinant nicotinic cholinergic receptors. Responses to ACh were blocked by linopirdine in both OHCs and inner hair cells (IHCs) of rats at postnatal days 21-27 (OHCs) and 9-11 (IHCs). In addition, linopirdine blocked responses of recombinant alpha9alpha10 nicotinic cholinergic receptors (nAChRs) in a concentration-dependent manner with an IC(50) of 5.2 microM. Block by linopirdine was readily reversible, voltage independent, and surmountable at high concentrations of ACh, thus suggestive of a competitive type of interaction with the receptor. The present results contribute to the pharmacological characterization of alpha9alpha10-containing nicotinic receptors and indicate that linopirdine should be used with caution when analyzing the cholinergic sensitivity of cochlear hair cells.
Art,
Synaptic hyperpolarization and inhibition of turtle cochlear hair cells.
1984, Pubmed
Art,
Synaptic hyperpolarization and inhibition of turtle cochlear hair cells.
1984,
Pubmed
Blanchet,
Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors.
1996,
Pubmed
Brownell,
Evoked mechanical responses of isolated cochlear outer hair cells.
1985,
Pubmed
Chen,
Differences in cholinergic responses from outer hair cells of rat and guinea pig.
1996,
Pubmed
,
Xenbase
Costa,
Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine: mechanism of action studies.
1997,
Pubmed
Dallos,
The active cochlea.
1992,
Pubmed
Dallos,
High-frequency motility of outer hair cells and the cochlear amplifier.
1995,
Pubmed
Dulon,
Cholinergic responses in developing outer hair cells of the rat cochlea.
1996,
Pubmed
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
Erostegui,
In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.
1994,
Pubmed
Evans,
Acetylcholine activates two currents in guinea-pig outer hair cells.
1996,
Pubmed
Eybalin,
Neurotransmitters and neuromodulators of the mammalian cochlea.
1993,
Pubmed
Fuchs,
Synaptic transmission at vertebrate hair cells.
1996,
Pubmed
Fuchs,
A novel cholinergic receptor mediates inhibition of chick cochlear hair cells.
1992,
Pubmed
Glowatzki,
Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.
2000,
Pubmed
Hiel,
Cloning and expression of the alpha9 nicotinic acetylcholine receptor subunit in cochlear hair cells of the chick.
2000,
Pubmed
,
Xenbase
Housley,
Direct measurement of the action of acetylcholine on isolated outer hair cells of the guinea pig cochlea.
1991,
Pubmed
Housley,
Ionic currents of outer hair cells isolated from the guinea-pig cochlea.
1992,
Pubmed
Kakehata,
Cellular mechanism of acetylcholine-induced response in dissociated outer hair cells of guinea-pig cochlea.
1993,
Pubmed
Kros,
Expression of a potassium current in inner hair cells during development of hearing in mice.
1998,
Pubmed
Kubisch,
KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.
1999,
Pubmed
,
Xenbase
Lamas,
Effects of a cognition-enhancer, linopirdine (DuP 996), on M-type potassium currents (IK(M)) and some other voltage- and ligand-gated membrane currents in rat sympathetic neurons.
1997,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Lustig,
Molecular cloning and mapping of the human nicotinic acetylcholine receptor alpha10 (CHRNA10).
2001,
Pubmed
Marcotti,
Developmental expression of the potassium current IK,n contributes to maturation of mouse outer hair cells.
1999,
Pubmed
Marcotti,
Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells.
2003,
Pubmed
Morley,
Developmental mRNA expression of the alpha10 nicotinic acetylcholine receptor subunit in the rat cochlea.
2002,
Pubmed
Morley,
Identification of the subunits of the nicotinic cholinergic receptors in the rat cochlea using RT-PCR and in situ hybridization.
1998,
Pubmed
Oliver,
Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic transmission at auditory outer hair cells.
2000,
Pubmed
Oliver,
Memantine inhibits efferent cholinergic transmission in the cochlea by blocking nicotinic acetylcholine receptors of outer hair cells.
2001,
Pubmed
,
Xenbase
Oliver,
Resting potential and submembrane calcium concentration of inner hair cells in the isolated mouse cochlea are set by KCNQ-type potassium channels.
2003,
Pubmed
Tsai,
The effect of 3,3-dipyridylmethyl-1-phenyl-2-indolinone on the neuromuscular transmission in the rodent skeletal muscles.
1992,
Pubmed
Vickroy,
Presynaptic cholinergic actions by the putative cognitive enhancing agent DuP 996.
1993,
Pubmed
Wang,
KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
1998,
Pubmed
,
Xenbase
Weisstaub,
The alpha9alpha10 nicotinic acetylcholine receptor is permeable to and is modulated by divalent cations.
2002,
Pubmed
,
Xenbase