Muscarinic acetylcholine receptor subtype expression in type vestibular hair cells of guinea pigs

Yao, Qi; Cheng, Hui; Guo, Chang-Kai; Zhou, Tao; Huang, Xiang; Kong, Weijia

doi:10.1007/s11596-011-0582-1

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…It is unclear where these putaLve M5mAChRs reside. Given its slower kineLcs and no obvious interacLons with the tradiLonal EVS-mediated slow excitaLon, it may not be expressed in afferents but in hair cells instead where changes in transmifer release could enhance excitability of the afferent (Derbenev et al, 2005;Holt et al, 2003;Li & Correia, 2011;Yao et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have demonstrated that all mulLple mAChR subtypes are present in the vesLbular end organs of guinea pigs, rat, and humans (Ishiyama et al, 1997;Li et al, 2007;Yao et al, 2011;Wackym et al, 1996). Thus far, pharmacological data and the presence of EVS-mediated slow excitaLon in M2/M4 double-KO mice suggest that M2 and M4mAChRs are not involved, while other pharmacological data implicate a major role for M3mAChRs and perhaps a minor role for M1mAChRs.…”

Section: Ac-va-on Of M5machrs Enhance the Background Firing Rate Of A...mentioning

confidence: 97%

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Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals

Sinha,

Lee,

Holt

2023

Preprint

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The peripheral vestibular system detects head position and movement through activation of vestibular hair cells (HCs) in vestibular end organs. HCs transmit this information to the CNS by way of primary vestibular afferent neurons. The CNS, in turn, modulates HCs and afferents via the efferent vestibular system (EVS) through activation of cholinergic signaling mechanisms. In mice, we previously demonstrated that activation of muscarinic acetylcholine receptors (mAChRs), during EVS stimulation, gives rise to a slow excitation that takes seconds to peak and tens of seconds to decay back to baseline. This slow excitation is mimicked by muscarine and ablated by the non-selective mAChR blockers scopolamine, atropine, and glycopyrrolate. While five distinct mAChRs (M1-M5) exist, the subtype(s) driving EVS-mediated slow excitation remain unidentified and details on how these mAChRs alter vestibular function is not well understood. The objective of this study is to characterize which mAChR subtypes drive the EVS-mediated slow excitation, and how their activation impacts vestibular physiology and behavior. In C57Bl/6J mice, M3mAChR antagonists were more potent at blocking slow excitation than M1mAChR antagonists, while M2/M4 blockers were ineffective. While unchanged in M2/M4mAChR double KO mice, EVS-mediated slow excitation in M3 mAChR-KO animals were reduced or absent in irregular afferents but appearing unchanged in regular afferents. In agreement, vestibular sensory-evoked potentials, known to originate from irregular afferents, were much less enhanced by mAChR activation in M3mAChR-KO mice compared to controls. Finally, M3mAChR-KO mice display distinct behavioral phenotypes in open field activity, and thermal profiles, and balance beam and forced swim test. M3mAChRs mediate efferent-mediated slow excitation in irregular afferents, while M1mAChRs may drive the same process in regular afferents.

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Section: Discussionmentioning

confidence: 99%

Section: Ac-va-on Of M5machrs Enhance the Background Firing Rate Of A...mentioning

confidence: 97%

Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals

Sinha,

Lee,

Holt

2023

Preprint

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“…The activation of mAChRs typically leads to downstream events with much slower kinetics than those occurring through nAChR activation. Based on singlecell RT-PCR studies, it was reported that mAChR subtypes M1-5 were all expressed in type II hair vestibular hair cells of the guinea pig (Yao et al 2011) and bird (Li et al 2007). However, only M1, M2, and M5 mAChRs have been detected in the human vestibular periphery (Wackym et al 1996).…”

Section: Muscarinic Acetylcholine Receptorsmentioning

confidence: 99%

A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications

Poppi

Holt

Lim

et al. 2020

Journal of Neurophysiology

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It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.

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“…Besides, m1, m2, m5mAChR subtypes have also been observed in human vestibular periphery by reverse transcription polymerase chain reaction (RT-PCR) studies [10,11]. Recently, immunohistochemical studies have further supported that m1-m5 mAChR subtypes were located in isolated VHCs II of pigeons [12], and RT-PCR has also provided strong evidence that m1-m5 mAChR subtypes were detected in isolated VHCs II of guinea pig [13]. …”

Section: Introductionmentioning

confidence: 99%

Two Distinct Channels Mediated by m2mAChR and α9nAChR Co-Exist in Type II Vestibular Hair Cells of Guinea Pig

Zhou

Wang

Guo

et al. 2013

IJMS

Self Cite

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Acetylcholine (ACh) is the principal vestibular efferent neurotransmitter among mammalians. Pharmacologic studies prove that ACh activates a small conductance Ca2+-activated K+ channels (KCa) current (SK2), mediated by α9-containing nicotinic ACh receptor (α9nAChR) in mammalian type II vestibular hair cells (VHCs II). However, our studies demonstrate that the m2 muscarinic ACh receptor (m2mAChR) mediates a big conductance KCa current (BK) in VHCs II. To better elucidate the correlation between these two distinct channels in VHCs II of guinea pig, this study was designed to verify whether these two channels and their corresponding AChR subtypes co-exist in the same VHCs II by whole-cell patch clamp recordings. We found that m2mAChR sensitive BK currents were activated in VHCs II isolated by collagenase IA, while α9nAChR sensitive SK2 currents were activated in VHCs II isolated by trypsin. Interestingly, after exposing the patched cells isolated by trypsin to collagenase IA for 3 min, the α9nAChR sensitive SK2 current was abolished, while m2mAChR-sensitive BK current was activated. Therefore, our findings provide evidence that the two distinct channels and their corresponding AChR subtypes may co-exist in the same VHCs II, and the alternative presence of these two ACh receptors-sensitive currents depended on isolating preparation with different enzymes.

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Muscarinic acetylcholine receptor subtype expression in type vestibular hair cells of guinea pigs

Cited by 5 publications

References 36 publications

Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals

Elucidating the role of muscarinic acetylcholine receptor (mAChR) signaling in efferent mediated responses of vestibular afferents in mammals

A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications

Two Distinct Channels Mediated by m2mAChR and α9nAChR Co-Exist in Type II Vestibular Hair Cells of Guinea Pig

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