Acetylcholine modulated potassium channel in the hair cell of the toadfish saccule

doi:10.1016/0378-5955(88)90123-2

Hearing Research

Volume 35, Issues 2–3, 15 September 1988, Pages 265-269

https://doi.org/10.1016/0378-5955(88)90123-2 Get rights and content

Abstract

Sensory transduction in the acoustic-lateralis system is modulated by an efferent synapse on the sensory hair cells and afferent fibers. Acetylcholine has been implicated as a neuro-transmitter at this synapse. This work addresses the ionic mechanism of action of acetylcholine on the hair cell of the toadfish saccule using path clamp methods and single channel recording. Acetylcholine and oxotremorine, a muscarinic agonist, were found to increase the open time and opening rate of a high conductance K⁺ channel in the basolateral walls of the hair cell. This effect is not dependent on the presence of Ca²⁺ in the extracellular media. The involvement of an intracellular mediator is implicated since bath applied agonist opens K⁺ channels isolated under the recording pipette.

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Cited by (26)

M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II vestibular hair cells
2012, Hearing Research
Citation Excerpt :
Different from the mAChR excitation mentioned above, previous studies of whole-cell recordings have suggested that mAChRs on non-mammalian VHCs are typically coupled with a hyperpolarization response. It has been found that application of ACh and oxotremorine (a muscarinic agonist) produced an increase in the open time and opening rate of a potassium channel in toadfish saccular hair cells (Steinacker and Rojas, 1988). Yoshida et al. (1994) demonstrated the presence of a G-protein-coupled, mAChR-mediated SK current located in the isolated frog saccular hair cells.
There are two types of hair cells in the sensory epithelium of vestibular end organ. Type II vestibular hair cell (VHC II) is innervated by the efferent nerve endings, which employ a cholinergic inhibition mediated by SK channels through the activation of α9-containing nAChR. Our previous studies demonstrated that a BK-type cholinergic inhibition was present in guinea pig VHCs II, which may be mediated by an unknown mAChR. In this study, BK channel activities triggered by ACh were studied to determine the mAChR subtype and function. We found the BK channel was insensitive to α9-containing nAChR antagonists and m1, m3, m4 muscarinic antagonists, but potently inhibited by the m2 muscarinic antagonist. Muscarinic agonists could mimic the effect of ACh and be blocked by m2 antagonist. cAMP analog activated the BK current and adenyl cyclase (AC) inhibitor inhibited the ACh response. Inhibitor of Giα subunit failed to affect the BK current, but inhibitor of Giα and Giβγ subunits showed a potent inhibition to these currents. Our findings provide the physiological evidence that mAChRs may locate in guinea pig VHCs II, and m2 mAChRs may play a dominant role in BK-type cholinergic inhibition. The activation of m2 mAChRs may stimulate Giβγ-mediated excitation of AC/cAMP activities and lead to the phosphorylation of Ca²⁺ channels, resulting in the influx of Ca²⁺ and opening of the BK channel.
The effect of proteolytic enzymes on the α9-nicotinic receptor-mediated response in isolated frog vestibular hair cells
2001, Hearing Research
In frog vestibular organs, efferent neurons exclusively innervate type II hair cells. Acetylcholine, the predominant efferent transmitter, acting on acetylcholine receptors of these hair cells ultimately inhibits and/or facilitates vestibular afferent firing. A coupling between α9-nicotinic acetylcholine receptors (α9nAChR) and apamin-sensitive, small-conductance, calcium-dependent potassium channels (SK) is thought to drive the inhibition by hyperpolarizing hair cells thereby decreasing their release of transmitter onto afferents. The presence of α9nAChR in these cells was demonstrated using pharmacological, immunocytochemical, and molecular biological techniques. However, fewer than 10% of saccular hair cells dissociated using protease VIII, protease XXIV, or papain responded to acetylcholine during perforated-patch clamp recordings. When present, these responses were invariably transient, small in amplitude, and difficult to characterize. In contrast, the majority of saccular hair cells (∼90%) dissociated using trypsin consistently responded to acetylcholine with an increase in outward current and concomitant hyperpolarization. In agreement with α9nAChR pharmacology obtained in other hair cells, the acetylcholine response in saccular hair cells was reversibly antagonized by strychnine, curare, tetraethylammonium, and apamin. Brief perfusions with either protease or papain permanently abolished the α9-nicotinic response in isolated saccular hair cells. These enzymes when inactivated became completely ineffective at abolishing the α9-nicotinic response, suggesting an enzymatic interaction with the α9nAChR and/or downstream effector. The mechanism by which these enzymes render saccular hair cells unresponsive to acetylcholine remains unknown, but it most likely involves proteolysis of α9nAChR, SK, or both.
Autoradiographic demonstration of quinuclidinyl benzilate binding sites in the vestibular organs of the gerbil
1999, Brain Research
Gerbil vestibular tissues were isolated by microdissection and incubated in vitro with $^{3} H$ -quinuclidinyl benzilate ( $^{3} H$ -QNB). Control tissues were incubated in medium containing unlabeled atropine to differentiate non-specific from specific binding. Autoradiographic grain densities were determined by morphometric techniques and evaluated by two-tailed t-test. The label densities of sensory epithelia from experimental preparations of ampulla, utricle and saccule were found to be significantly higher than those in the adjacent endolymphatic compartment and also higher than those of adjacent stromal tissue comprising connective tissue, nerve fibers and capillaries. In contrast, no tissue region in atropine controls showed label density significantly above that of the endolymphatic compartment. Label density of ampullar sensory epithelium incubated with $^{3} H$ -QNB alone was significantly higher than that of sensory epithelium from utricle or saccule. Grain density was greater in the peripheral regions of the ampullar crista compared to the vertex. Appreciable label was also present in nerve bundles beneath the sensory epithelium of the ampulla. The current study demonstrates the existence of putative muscarinic neurotransmitter/neuromodulator receptor sites in mammalian vestibular sense organs at locations corresponding to efferent innervation, with particularly significant concentrations in the ampulla.
The vestibular hair cells: Post-transductional signal processing
1998, Progress in Neurobiology
Hair cells in mechanosensory systems transduce mechanical stimuli into biological signals to be presented to and analyzed by the brain. Vestibular hair cells transduce stimuli primarily associated with the organism's orientation and motion in space. When examined superficially it may appear that the hair cells act as passive transducers whereby mechanical stimulation of their hair bundle results in transmitter release at their afferent synapses. In fact, hair cell functions are more complicated, and the mechanical signals are heavily processed even before being encoded in afferent nerve activity. Hair cells are different from one another in morphology, biophysics, transmitter and transmitter receptor complements, not only across different organs (as one might expect), but even in the same organ. This review focuses on hair cell morpho-physiological properties, ionic conductances, neurotransmitters/modulators and their receptors, second messengers and effectors. Special features of hair cell neurotransmission, as the synaptic body and the presence of autoreceptors and local circuits, are also discussed, as is the possibility of a differential modulation of hair cell transmitter release in the resting and mechanically-stimulated states.
The hair cell acetylcholine receptors: A synthesis
1996, Hearing Research
In this article the evidence concerning the nature of the acetylcholine (ACh) receptors on hair cells is reviewed. A schematic organization of these receptors is offered, based on the evidence as follows. (1) There are two kinds of ACh receptors on hair cells: muscarinic-like and nicotinic-like. (2) The nicotinic-like receptor mediates a hyperpolarizing response to ACh and a consequent reduction in afferent firing. (3) The muscarinic-like receptors mediate both a depolarization and a hyperpolarization of hair cells. (4) The hyperpolarization results in a reduction in afferent firing and (5) the depolarization results in an increase in afferent firing.
Chemical synaptic transmission in the cochlea
1995, Progress in Neurobiology
The last two decades have witnessed major progress in the understanding of cochlear mechanical functioning, and in the emergence of cochlear neurochemistry and neuropharmacology. Recent models describe active processes within the cochlea that amplify and sharpen the mechanical response to sound. Although it is widely accepted that outer hair cells (OHCs) contribute to these processes, the nature of the medial efferent influence on cochlear mechanics needs further clarification. Acetylcholine (ACh) is the major transmitter released onto OHCs during the stimulation of these efferents. The inhibitory influence of this system is mediated by post- and presynaptic nicontinic and muscarinic receptors and the role of other neuroactive substances [γ-aminobutyric acid (GABA), calcitonin gene-related peptide (CGRP), adenosine 5′-triphosphate (ATP) or nitric oxide (NO)] remains to be determined. The inner hair cells (IHCs) that transduce the mechanical displacements into neural activity, release glutamate on receptor-activated channels of AMPA, kainate, and NMDA types. This synapse is in turn controlled and/or regulated by the lateral efferents containing a cocktail of neuroactive substances (ACh, GABA, dopamine, enkephalins, dynorphin, CGRP). This glutamatergic nature of the IHCs is responsible for the acute destruction of the nerve endings and subsequently for neuronal death, damage usually described in various cochlear diseases (noise-induced hearing losses, neural presbycusis and certain forms of sudden deafness or peripheral tinnitus). These pathologies also include a regrowth of new dendritic processes by surviving neurons up to IHCs. Understanding the subtle molecular mechanisms which underly the control of neuronal excitability, synaptic plasticity and neuronal death in cochlear function and disease is a very important issue for the development of future therapies.

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Abstract

References (24)

Localization of enkephalin-like immunoreactivity in acetylcholinesterase-positive cells in the guinea pig lateral superior olivary complex that project to the cochlea

Neurosci.

Variation of membrane properties in hair cells isolated from the turtle cochlea

J. Physiol.

Efferent regulation of hair cells in the turle cochlea

Synaptic hyperpolarization and inhibition of cochlear hair cells in the turtle Pseudemys Scripta elegans

J. Physiol.

Efferent modulation of hair cell tuning in the cochlea of the turtle

J. Physiol.

Effects of efferent nerve stimulation on hair cells of frog sacculus

J. Physiol.

Presynaptic actions of cholinergic agents upon the hair cell-afferent fiber synapse in the vestibular labyrinth of the frog

Brain Res.

Action of cholinergic and anticholinergic drugs at the crossed olivocochlear bundle-hair cell junction

Acta Oto-Laryngol. (Stockh.)

Cholinergic organization in the brain of a sound producing fish: a choline acetyltransferase study

J. Comp. Neurol.

The post-synaptic action of efferent fibres in the lateral line organ of the burbot Lota lota

J. Physiol.

Inhibition by efferent nerve fibres: action on hair cells and efferent synaptic transmission in the lateral line canal organ of the burbot Lota lota

J. Physiol.

Effects of efferent stimulation on the saccule of goldfish

J. Physiol.

Cited by (26)

M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II vestibular hair cells

The effect of proteolytic enzymes on the α9-nicotinic receptor-mediated response in isolated frog vestibular hair cells

Autoradiographic demonstration of quinuclidinyl benzilate binding sites in the vestibular organs of the gerbil

The vestibular hair cells: Post-transductional signal processing

The hair cell acetylcholine receptors: A synthesis

Chemical synaptic transmission in the cochlea

Short communicationAcetylcholine modulated potassium channel in the hair cell of the toadfish saccule

Abstract

Neurosci.

Variation of membrane properties in hair cells isolated from the turtle cochlea

J. Physiol.

Efferent regulation of hair cells in the turle cochlea

Synaptic hyperpolarization and inhibition of cochlear hair cells in the turtle Pseudemys Scripta elegans

J. Physiol.

Efferent modulation of hair cell tuning in the cochlea of the turtle

J. Physiol.

Effects of efferent nerve stimulation on hair cells of frog sacculus

J. Physiol.

Presynaptic actions of cholinergic agents upon the hair cell-afferent fiber synapse in the vestibular labyrinth of the frog

Brain Res.

Action of cholinergic and anticholinergic drugs at the crossed olivocochlear bundle-hair cell junction

Acta Oto-Laryngol. (Stockh.)

Cholinergic organization in the brain of a sound producing fish: a choline acetyltransferase study

J. Comp. Neurol.

The post-synaptic action of efferent fibres in the lateral line organ of the burbot Lota lota

J. Physiol.

Inhibition by efferent nerve fibres: action on hair cells and efferent synaptic transmission in the lateral line canal organ of the burbot Lota lota

J. Physiol.

Effects of efferent stimulation on the saccule of goldfish

J. Physiol.

Short communication
Acetylcholine modulated potassium channel in the hair cell of the toadfish saccule