Unique Postsynaptic Signaling at the Hair Cell Efferent Synapse Permits Calcium to Evoke Changes on Two Time Scales

Sridhar, T.S.; Brown, M. Christian; Sewell, William F.

doi:10.1523/jneurosci.17-01-00428.1997

Cited by 139 publications

(126 citation statements)

References 37 publications

(51 reference statements)

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…At this location they adjoin a restricted (Ͻ20 nm wide), essentially planar diffusion space formed by the extensively parallel cisternal and plasma membranes . Influx through the hair cell AChRs should raise calcium to high levels in this subcisternal space, independent of additional calcium that might be released from the synaptic cistern during prolonged activity (Sridhar et al, 1997;Lioudyno et al, 2004). This calcium signal is sufficient to activate SK and BK channels, even without an accompanying depolarization.…”

Section: Discussionmentioning

confidence: 99%

Activation of BK and SK Channels by Efferent Synapses on Outer Hair Cells in High-Frequency Regions of the Rodent Cochlea

et al. 2015

View full text Add to dashboard Cite

Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and associated calcium-activated potassium channels. Although inhibition was thought to involve exclusively small conductance (SK potassium channels), recent findings have shown that BK channels also contribute to inhibition in basal, highfrequency OHCs after the onset of hearing. Here we show that the waveform of randomly timed IPSCs (evoked by high extracellular potassium) in high-frequency OHCs is altered by blockade of either SK or BK channels, with BK channels supporting faster synaptic waveforms and SK channels supporting slower synaptic waveforms. Consistent with these findings, IPSCs recorded from high-frequency OHCs that express BK channels are briefer than IPSCs recorded from low-frequency (apical) OHCs that do not express BK channels and from immature high-frequency OHCs before the developmental onset of BK channel expression. Likewise, OHCs of BK␣ Ϫ/Ϫ mice lacking the pore-forming ␣-subunit of BK channels have longer IPSCs than do the OHCs of BK␣ ϩ/ϩ littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BK␣ Ϫ/Ϫ OHCs were smaller than those of BK␣ ϩ/ϩ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BK␣ Ϫ/Ϫ OHCs were smaller than those of BK␣ ϩ/ϩ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of BK and SK Channels by Efferent Synapses on Outer Hair Cells in High-Frequency Regions of the Rodent Cochlea

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Because of the slow kinetics involved, it is natural to suspect metabotropic receptors. At the same time, it should be noted that fast and slow efferent effects in the mammalian cochlea may involve the same nicotinic receptor (Sridhar et al 1995(Sridhar et al , 1997. Efferent neurons contain CGRP (Tanaka et al 1988(Tanaka et al , 1989Wackym et al 1991;Ishiyama et al 1994) and possibly other neuroactive peptides (for review, see Goldberg et al 1999).…”

Section: Fast and Slow Responsesmentioning

confidence: 99%

Efferent Actions in the Chinchilla Vestibular Labyrinth

Marlinski

Plotnik

Goldberg

2004

JARO

View full text Add to dashboard Cite

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.

show abstract

“…For example, in the hair cell efferent synapses of the mammalian cochlea, nAChRs suppress sound-evoked activity of the auditory nerve on a millisecond time scale, mediated by activation of calcium-activated potassium channels by calcium flux through nAChR channels. In addition, there is a slower inhibition over tens of seconds, which is mediated by CICR upon nAChR activation (Sridhar et al, 1997). Thus, this downstream calcium signaling mechanism allows regulation of two temporally distinct processes by the activation of nAChRs.…”

Section: Downstream Activation Mechanismsmentioning

confidence: 99%

Nicotinic receptor signaling in nonexcitable cells

2002

View full text Add to dashboard Cite

ABSTRACT:The finding that neuronal nicotinic acetylcholine receptors (nAChRs) are present in nonneuronal cells both within and outside the nervous system raises some interesting issues. The mechanisms underlying receptor signaling and its downstream consequences in these cells remain to be elucidated. Factors controlling the release of acetylcholine and the extent of its diffusion are likely to be different for these cells than for traditional neuronal synapses. Recent advances on the physiologic functions of some of these cell types have provided a better insight into possible functional roles for nAChRs in nonexcitable cells. The presence of nAChRs on these cells also implies a broader scope for the actions of nicotine that needs to be considered from a clinical viewpoint. Revealing the potential physiologic roles for nAChRs on nonexcitable cells is likely to provide a more complete understanding of cholinergic signaling.

show abstract

Unique Postsynaptic Signaling at the Hair Cell Efferent Synapse Permits Calcium to Evoke Changes on Two Time Scales

Cited by 139 publications

References 37 publications

Activation of BK and SK Channels by Efferent Synapses on Outer Hair Cells in High-Frequency Regions of the Rodent Cochlea

Activation of BK and SK Channels by Efferent Synapses on Outer Hair Cells in High-Frequency Regions of the Rodent Cochlea

Efferent Actions in the Chinchilla Vestibular Labyrinth

Nicotinic receptor signaling in nonexcitable cells

Contact Info

Product

Resources

About