Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea

Kevin N. Rohmann, Eric Wersinger, Jeremy P. Braude, Sonja J. Pyott, Paul Albert Fuchs

Research output: Contribution to journalArticle

Abstract

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 ofBKchannel expression. Likewise, OHCs ofBKα-/-mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα+/+littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα-/- OHCs were smaller than those of BKα+/+ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα-/- OHCs were smaller than those of BKα+/+ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.

Original languageEnglish (US)
Pages (from-to)1821-1830
Number of pages10
JournalJournal of Neuroscience
Volume35
Issue number5
DOIs
StatePublished - 2015

Fingerprint

Outer Auditory Hair Cells
Large-Conductance Calcium-Activated Potassium Channels
Cochlea
Synapses
Rodentia
Small-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels

Keywords

  • BK channel
  • Cholinergic inhibition
  • Cochlea
  • Efferent inhibition
  • Outer hair cell
  • SK channel

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea. / Rohmann, Kevin N.; Wersinger, Eric; Braude, Jeremy P.; Pyott, Sonja J.; Fuchs, Paul Albert.

In: Journal of Neuroscience, Vol. 35, No. 5, 2015, p. 1821-1830.

Research output: Contribution to journalArticle

Rohmann, Kevin N. ; Wersinger, Eric ; Braude, Jeremy P. ; Pyott, Sonja J. ; Fuchs, Paul Albert. / Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 5. pp. 1821-1830.
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abstract = "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 ofBKchannel expression. Likewise, OHCs ofBKα-/-mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα+/+littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα-/- OHCs were smaller than those of BKα+/+ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα-/- OHCs were smaller than those of BKα+/+ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.",
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AU - Rohmann, Kevin N.

AU - Wersinger, Eric

AU - Braude, Jeremy P.

AU - Pyott, Sonja J.

AU - Fuchs, Paul Albert

PY - 2015

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N2 - 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 ofBKchannel expression. Likewise, OHCs ofBKα-/-mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα+/+littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα-/- OHCs were smaller than those of BKα+/+ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα-/- OHCs were smaller than those of BKα+/+ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.

AB - 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 ofBKchannel expression. Likewise, OHCs ofBKα-/-mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα+/+littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα-/- OHCs were smaller than those of BKα+/+ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα-/- OHCs were smaller than those of BKα+/+ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.

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