Gating of Ca2+-Activated K+ Channels Controls Fast Inhibitory Synaptic Transmission at Auditory Outer Hair Cells

Oliver, Dominik; Klöcker, Nikolaj; Schuck, Jochen; Baukrowitz, Thomas; Ruppersberg, J. P.; Fakler, Bernd

doi:10.1016/s0896-6273(00)81197-6

Cited by 233 publications

(314 citation statements)

References 31 publications

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“…The synaptic basis of efferent inhibition has now been worked out (Fuchs and Murrow 1992a, b). Inhibition takes place in hair cells and is the result of the activation of a9/10 nicotinic channels (Elgoyhen et al 2001), whose opening allows the entry of Ca 2+ ions (Weisstaub et al 2000) and the activation of calcium-activated K + channels of the SK variety (Oliver et al 2000). Outward currents through the SK channel hyperpolarize the hair cell and inhibit neurotransmitter release.…”

Section: Excitatory Nature Of the Responsesmentioning

confidence: 99%

Efferent Actions in the Chinchilla Vestibular Labyrinth

Marlinski

Plotnik

Goldberg

2004

JARO

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Efferent fibers were electrically stimulated in the brain stem, while afferent activity was recorded from the superior vestibular nerve in barbiturate-anesthetized chinchillas. We concentrated on canal afferents, but otolith afferents were also studied. Among canal fibers, calyx afferents were recognized by their irregular discharge and low rotational gains. In separate experiments, stimulating electrodes were placed in the efferent cell groups ipsilateral or contralateral to the recording electrode or in the midline. While single shocks were ineffective, repetitive shock trains invariably led to increases in afferent discharge rate. Such excitatory responses consisted of fast and slow components. Fast components were large only at high shock frequencies (200-333/s), built up with exponential time constants <0.1 s, and showed response declines or adaptation during shock trains >1 s in duration. Slow responses were obtained even at shock rates of 50/s, built up and decayed with time constants of 15-30 s, and could show little adaptation. The more regular the discharge, the larger was the efferent response of an afferent fiber. Response magnitude was proportional to cv* b , a normalized coefficient of interspike-interval variation (cv*) raised to the power b = 0.7. The value of the exponent b did not depend on unit type (calyx vs. bouton plus dimorphic, canal vs. otolith) or on stimulation site (ipsilateral, contralateral, or midline). Responses were slightly smaller with contralateral or midline stimulation than with ipsilateral stimulation, and they were smaller for otolith, as compared to canal, fibers.An anatomical study had suggested that responses to contralateral afferent stimulation should be small or nonexistent in irregular canal fibers. The suggestion was not confirmed in this study. Contralateral responses, including the large responses typically seen in irregular fibers, were abolished by shallow midline incisions that should have severed crossing efferent axons.

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Section: Excitatory Nature Of the Responsesmentioning

confidence: 99%

Efferent Actions in the Chinchilla Vestibular Labyrinth

Marlinski

Plotnik

Goldberg

2004

JARO

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“…Similar chaperon proteins have not been described in the case of α9α10 receptors. However, it is known that activation of the α9α10 nAChR leads to an increase in intracellular Ca 2+ and the subsequent opening of small conductance Ca 2+ -activated K + SK channels, thus leading to hyperpolarization of hair cells (Dulon et al 1998;Fuchs and Murrow 1992;Housley and Ashmore 1991;Oliver et al 2000). Moreover, SK channels and α9α10 are known to co-localize in the same functional microdomain, and through such close coupling, the gating kinetics of the SK channels determine the time course of synaptic action, outlasting the driving calcium signals (Oliver et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is known that activation of the α9α10 nAChR leads to an increase in intracellular Ca 2+ and the subsequent opening of small conductance Ca 2+ -activated K + SK channels, thus leading to hyperpolarization of hair cells (Dulon et al 1998;Fuchs and Murrow 1992;Housley and Ashmore 1991;Oliver et al 2000). Moreover, SK channels and α9α10 are known to co-localize in the same functional microdomain, and through such close coupling, the gating kinetics of the SK channels determine the time course of synaptic action, outlasting the driving calcium signals (Oliver et al 2000). In addition, through the generation of a KCNN2 (gene coding for the SK2 protein) knockout mice, it has been demonstrated recently that the KCNN2 gene is solely responsible for encoding this class of small conductance, calciumactivated potassium channel in cochlear hair cells (Johnson et al 2007;Kong et al 2008) and that it cannot be replaced by the later developmental arrival of rapidly activating, iberiotoxin-sensitive "BK"-type potassium channels shown in mammals (Hafidi et al 2005;Kros et al 1998;Langer et al 2003) and birds (Fuchs and Sokolowski 1990).…”

Section: Discussionmentioning

confidence: 99%

“…C RT-PCR from transgenic cochleae indicating a positive band of 446 bp in transgenic mice using amplimers that anneal at the α10 cDNA and the FLAG sequence (gray arrows in A). were essentially as described previously (Glowatzki and Fuchs 2000;Oliver et al 2000).…”

Section: Electrophysiological Recordings From Cochlear Hair Cellsmentioning

confidence: 99%

“…Activation of this pathway reduces cochlear sensitivity through the action of ACh on nicotinic receptors (nAChRs) at the base of OHCs. Significant progress has been made in defining the cellular mechanisms of hair cell inhibition: α9 and α10 nAChR subunits arrange into a pentameric assembly with a likely (α9) 2 (α10) 3 stoichiometry (Elgoyhen et al 1994(Elgoyhen et al , 2001Lustig et al 2001;Plazas et al 2005;Sgard et al 2002) and activation of the α9α10 nAChR leads to an increase in intracellular Ca 2+ and the subsequent opening of small conductance Ca 2+ -activated K + (SK2) channels, thus leading to hyperpolarization of hair cells (Dulon et al 1998;Fuchs and Murrow 1992;Housley and Ashmore 1991;Oliver et al 2000).…”

Section: Introductionmentioning

confidence: 99%

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Constitutive Expression of the α10 Nicotinic Acetylcholine Receptor Subunit Fails to Maintain Cholinergic Responses in Inner Hair Cells After the Onset of Hearing

Taranda

Ballestero

Hiel

et al. 2009

JARO

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Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 −/− background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental downregulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh.

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Nicotinic Acetylcholine Receptors

Colquhoun

Shelley

Hatton

et al. 2003

Burger's Medicinal Chemistry and Drug Discovery

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Nicotinic receptors are cation-permeable ion channels activated by the neurotransmitter acetylcholine The muscle type receptor mediates all fast synaptic excitation on voluntary muscle. We review both the structure and the function of muscle/Torpedo receptor, and the function of several mutants. Recent developments in both knowledge of structure, and in analysis of single channel records, are beginning to throw light on the role of single amino acid residues in the molecular events (the binding of an agonist and the gating of the channel) that lead to channel opening. In the nervous system, nicotinic channels mediate the majority of fast excitation only in autonomic ganglia, but are also present at presynaptic locations. Issues of receptor classification and subunit composition are particularly relevant for neuronal channels, because of the numerous subunit combinations possible and because relatively few selective competitive antagonists are available, a situation that may improve with the characterisation of alpha-conotoxins. Inherited mutations in nicotinic channels gives rise to rare congenital forms of human disease (myasthenia for muscle and epilepsy for neuronal receptors).

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Gating of Ca2+-Activated K+ Channels Controls Fast Inhibitory Synaptic Transmission at Auditory Outer Hair Cells

Cited by 233 publications

References 31 publications

Efferent Actions in the Chinchilla Vestibular Labyrinth

Efferent Actions in the Chinchilla Vestibular Labyrinth

Constitutive Expression of the α10 Nicotinic Acetylcholine Receptor Subunit Fails to Maintain Cholinergic Responses in Inner Hair Cells After the Onset of Hearing

Nicotinic Acetylcholine Receptors

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