Differential expression of α2–7, α9 and β2–4 nicotinic acetylcholine receptor subunit mRNA in the vestibular end-organs and Scarpa's ganglia of the rat

Anderson, Amy D.; Troyanovskaya, Marta; Wackym, Phillip A.

doi:10.1016/s0006-8993(97)01121-9

Cited by 51 publications

(32 citation statements)

References 23 publications

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“…This proposal was consistent with previous pharmacological characterization of ␣4␤2 nAChRs Chavez-Noriega et al, 1997;Iturriaga-Vásquez et al, 2010), as well as the expression of ␣4 and ␤2 nAChR subunits in primary vestibular neurons Zoli et al, 1995;Hiel et al, 1996;Anderson et al, 1997). Furthermore, in this study, the sensitivity of efferent-mediated excitation in CD afferents to varenicline, SazA, and 5-iodo was also consistent with ␣4␤2 nAChR pharmacology (Mukhin et al, 2000;Coe et al, 2005;Xiao et al, 2006;.…”

Section: Insight Into Subunit Composition Of Nachrs On CD Afferentssupporting

confidence: 92%

“…First, ␣-CtxMII is a potent antagonist of ␣6␤2* as well as ␣3␤2* nAChRs (Cartier et al, 1996;Kuryatov et al, 2000;. Although the ␣3 and ␤2 subunits are expressed by vestibular ganglia (Zoli et al, 1995;Hiel et al, 1996;Anderson et al, 1997), the estimated IC 50 values for DH␤E and bPiDDB in blocking ␣3␤2* nAChRs are in the micromolar range, suggesting that this subclass of nAChRs is unlikely to account for the ␣-CtxMII sensitivity of efferent-mediated excitation in turtle CD afferents (Chavez-Noriega et al, 1997;Endo et al, 2005;Rahman et al, 2008). One note of caution in making the argument for ␣6␤2* over ␣3␤2* is that it is predicated on turtle and mammalian ␣3␤2* nAChRs having comparable pharmacological profiles.…”

Section: Insight Into Subunit Composition Of Nachrs On CD Afferentsmentioning

confidence: 99%

“…The simplest interpretation of these pharmacological data is that efferent-mediated afferent excitation uses nAChRs distinct from ␣9␣10. To this end, ISH and RT-PCR studies have implicated a number of other nAChR subunits in vestibular ganglia and end organs Zoli et al, 1995;Hiel et al, 1996;Anderson et al, 1997). However, labeling with ␣9 antibodies and ␣BTX, as well as recent pharmacological data, suggests that afferent processes also express ␣9␣10 nAChRs Dailey et al, 2000;Luebke et al, 2005;Yu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

Holt

Kewin²,

Jordan³

et al. 2015

J. Neurosci.

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Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from ␣9␣10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton afferents. We recorded from CD and bouton afferents innervating the turtle posterior crista during electrical stimulation of vestibular efferents while applying several subtype-selective nAChR agonists and antagonists. The ␣9␣10 nAChR antagonists, ␣-bungarotoxin and ␣-conotoxin RgIA, blocked efferent-mediated inhibition in bouton afferents while leaving efferent-mediated excitation in CD units largely intact. Conversely, 5-iodo-A-85380, sazetidine-A, varenicline, ␣-conotoxin MII, and bPiDDB (N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide) blocked efferent-mediated excitation in CD afferents without affecting efferent-mediated inhibition in bouton afferents. This pharmacological profile suggested that calyceal nAChRs contain ␣6 and ␤2, but not ␣9, nAChR subunits. Selective blockade of efferent-mediated excitation in CD afferents distinguished dimorphic from calyx afferents by revealing type II hair cell input. Dimorphic afferents differed in having higher mean discharge rates and a mean efferentmediated excitation that was smaller in amplitude yet longer in duration. Molecular biological data demonstrated the expression of ␣9 in turtle hair cells and ␣4 and ␤2 in associated vestibular ganglia.

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Section: Insight Into Subunit Composition Of Nachrs On CD Afferentssupporting

confidence: 92%

Section: Insight Into Subunit Composition Of Nachrs On CD Afferentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

Holt

Kewin²,

Jordan³

et al. 2015

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Consistent with this observation, calyx endings were labeled with ␣-BTX Wackym et al, 1995;Dailey et al, 2000). Conversely, in situ hybridization studies, although failing to detect either ␣9 (Hiel et al, 1996) or ␣10 (Elgoyhen et al, 2001) mRNA in Scarpa's ganglion cells, did find mRNA expression for other nAChR subunits Hiel et al, 1996;Anderson et al, 1997). Our data indicate the postsynaptic presence of another nicotinic receptor, possibly in addition to ␣9/␣10.…”

Section: Postsynaptic Excitation Involves Nicotinic Receptors Other Tsupporting

confidence: 82%

Mechanisms of Efferent-Mediated Responses in the Turtle Posterior Crista

2006

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“…In addition, DMPP has been shown to activate ␣9nAChR in guinea pig outer hair cells (Erostegui et al 1994). However, dTC is not selective for ␣9nAChR exclusively, and since several nicotinic receptor subunit mRNAs other than ␣9 and ␣10 have been demonstrated in vestibular endorgans (Anderson et al 1997), it is uncertain whether the fast excitation and inhibition involve the same nicotinic ACh receptor or not. In this study, we compared the pharmacological and electrophysiological profile of this DMPP-sensitive, excitatory vestibular nicotinic ACh receptor to that of ␣9nAChR.…”

Section: Introductionmentioning

confidence: 99%

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

Holt

Lioudyno

Guth

2003

Journal of Neurophysiology

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A pharmacologically distinct nicotinic ACh receptor is found in a subset of frog semicircular canal hair cells. J Neurophysiol 90: 1526 -1536, 2003; 10.1152/jn.00273.2002. Frog vestibular organs are endowed with a prominent cholinergic efferent innervation whose stimulation results in several different effects, thereby suggesting diversity in the expression of postsynaptic acetylcholine (ACh) receptors. The application of ACh can mimic efferent stimulation in producing both an inhibition and a facilitation of afferent discharge which are thought to be mediated by at least two distinct ACh receptors present on vestibular hair cells, i.e., ␣9-containing nicotinic receptors (␣9nAChR) and muscarinic receptors (mAChR), respectively. Using patch-clamp and multiunit vestibular afferent recordings, we demonstrate the presence of an additional excitatory hair cell nicotinic ACh receptor pharmacologically distinct from both ␣9nAChR and mAChR. In order of increasing potency, this distinct receptor was activated by ACh, carbachol, and particularly by the selective nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP). This DMPP-sensitive nicotinic receptor (R DMPP ) was antagonized by the classic nicotinic antagonist d-tubocurarine, but refractory to strychnine, atropine, and propylbenzilylcholine mustard, at concentrations that completely block ␣9nAChR and/or mAChR. Activation of R DMPP on application of ACh or DMPP to a subpopulation of isolated posterior semicircular canal (SCC) hair cells resulted in a large depolarization (18.0 Ϯ 1.2 mV). The current underlying this depolarization was typically small (80.1 Ϯ 21.6 pA) and showed an inward rectification starting around Ϫ45 mV. Given their respective EC 50 s (47 nM vs. 20 M), R DMPP was nearly 400 times more sensitive to ACh than ␣9nAChR and thus responded to concentrations of ACh considered too low to be effective at stimulating ␣9nAChR. Despite this remarkable sensitivity, exogenous ACh readily stimulated the mAChR in the intact posterior SCC preparation but failed to activate R DMPP unless the acetylcholinesterase inhibitor physostigmine was present, or high concentrations of ACh were used (Ͼ3 mM). In frog, R DMPP most likely underlies the rapid excitatory response seen during efferent stimulation.

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Differential expression of α2–7, α9 and β2–4 nicotinic acetylcholine receptor subunit mRNA in the vestibular end-organs and Scarpa's ganglia of the rat

Cited by 51 publications

References 23 publications

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

Mechanisms of Efferent-Mediated Responses in the Turtle Posterior Crista

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

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