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Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse
Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110028/ https://www.ncbi.nlm.nih.gov/pubmed/35510987 http://dx.doi.org/10.7554/eLife.75219 |
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author | Richardson, Amy Ciampani, Victoria Stancu, Mihai Bondarenko, Kseniia Newton, Sherylanne Steinert, Joern R Pilati, Nadia Graham, Bruce P Kopp-Scheinpflug, Conny Forsythe, Ian D |
author_facet | Richardson, Amy Ciampani, Victoria Stancu, Mihai Bondarenko, Kseniia Newton, Sherylanne Steinert, Joern R Pilati, Nadia Graham, Bruce P Kopp-Scheinpflug, Conny Forsythe, Ian D |
author_sort | Richardson, Amy |
collection | PubMed |
description | Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse. |
format | Online Article Text |
id | pubmed-9110028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-91100282022-05-17 Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse Richardson, Amy Ciampani, Victoria Stancu, Mihai Bondarenko, Kseniia Newton, Sherylanne Steinert, Joern R Pilati, Nadia Graham, Bruce P Kopp-Scheinpflug, Conny Forsythe, Ian D eLife Neuroscience Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse. eLife Sciences Publications, Ltd 2022-05-05 /pmc/articles/PMC9110028/ /pubmed/35510987 http://dx.doi.org/10.7554/eLife.75219 Text en © 2022, Richardson et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Richardson, Amy Ciampani, Victoria Stancu, Mihai Bondarenko, Kseniia Newton, Sherylanne Steinert, Joern R Pilati, Nadia Graham, Bruce P Kopp-Scheinpflug, Conny Forsythe, Ian D Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title | Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title_full | Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title_fullStr | Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title_full_unstemmed | Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title_short | Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
title_sort | kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110028/ https://www.ncbi.nlm.nih.gov/pubmed/35510987 http://dx.doi.org/10.7554/eLife.75219 |
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