Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses
Summary: A Ca2+ current transient block (ICaTB) by protons occurs at some ribbon-type synapses after exocytosis, but this has not been observed at mammalian hair cells. Here we show that a robust ICaTB occurs at post-hearing mouse and gerbil inner hair cell (IHC) synapses, but not in immature IHC sy...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-12-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718318485 |
| _version_ | 1828848324365516800 |
|---|---|
| author | Philippe F.Y. Vincent Soyoun Cho Margot Tertrais Yohan Bouleau Henrique von Gersdorff Didier Dulon |
| author_facet | Philippe F.Y. Vincent Soyoun Cho Margot Tertrais Yohan Bouleau Henrique von Gersdorff Didier Dulon |
| author_sort | Philippe F.Y. Vincent |
| collection | DOAJ |
| description | Summary: A Ca2+ current transient block (ICaTB) by protons occurs at some ribbon-type synapses after exocytosis, but this has not been observed at mammalian hair cells. Here we show that a robust ICaTB occurs at post-hearing mouse and gerbil inner hair cell (IHC) synapses, but not in immature IHC synapses, which contain non-compact active zones, where Ca2+ channels are loosely coupled to the release sites. Unlike ICaTB at other ribbon synapses, ICaTB in mammalian IHCs displays a surprising multi-peak structure that mirrors the EPSCs seen in paired recordings. Desynchronizing vesicular release with intracellular BAPTA or by deleting otoferlin, the Ca2+ sensor for exocytosis, greatly reduces ICaTB, whereas enhancing release synchronization by raising Ca2+ influx or temperature increases ICaTB. This suggests that ICaTB is produced by fast multivesicular proton-release events. We propose that ICaTB may function as a submillisecond feedback mechanism contributing to the auditory nerve’s fast spike adaptation during sound stimulation. : Mature inner hair cells in the cochlea contain compact active zones where clustered Ca2+ channels are tightly coupled to the sites of vesicle fusion. Vincent et al. show that vesicle exocytosis leads to the release of protons into the synaptic cleft, which transiently blocks a subset of Ca2+ channels. Keywords: Ca2+ channels, pH buffering, protons, inner hair cells, ribbon synapses, exocytosis, otoferlin, auditory nerve fiber |
| first_indexed | 2024-12-12T22:27:34Z |
| format | Article |
| id | doaj.art-70812dc1c6a64df6b033b6d258261cf8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T22:27:34Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-70812dc1c6a64df6b033b6d258261cf82022-12-22T00:09:42ZengElsevierCell Reports2211-12472018-12-01251234513464.e3Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon SynapsesPhilippe F.Y. Vincent0Soyoun Cho1Margot Tertrais2Yohan Bouleau3Henrique von Gersdorff4Didier Dulon5Université de Bordeaux, Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Inserm U1120, 33076 Bordeaux, FranceCenter for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE 68131, USA; The Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USAUniversité de Bordeaux, Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Inserm U1120, 33076 Bordeaux, FranceUniversité de Bordeaux, Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Inserm U1120, 33076 Bordeaux, FranceThe Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA; Corresponding authorUniversité de Bordeaux, Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Inserm U1120, 33076 Bordeaux, France; Corresponding authorSummary: A Ca2+ current transient block (ICaTB) by protons occurs at some ribbon-type synapses after exocytosis, but this has not been observed at mammalian hair cells. Here we show that a robust ICaTB occurs at post-hearing mouse and gerbil inner hair cell (IHC) synapses, but not in immature IHC synapses, which contain non-compact active zones, where Ca2+ channels are loosely coupled to the release sites. Unlike ICaTB at other ribbon synapses, ICaTB in mammalian IHCs displays a surprising multi-peak structure that mirrors the EPSCs seen in paired recordings. Desynchronizing vesicular release with intracellular BAPTA or by deleting otoferlin, the Ca2+ sensor for exocytosis, greatly reduces ICaTB, whereas enhancing release synchronization by raising Ca2+ influx or temperature increases ICaTB. This suggests that ICaTB is produced by fast multivesicular proton-release events. We propose that ICaTB may function as a submillisecond feedback mechanism contributing to the auditory nerve’s fast spike adaptation during sound stimulation. : Mature inner hair cells in the cochlea contain compact active zones where clustered Ca2+ channels are tightly coupled to the sites of vesicle fusion. Vincent et al. show that vesicle exocytosis leads to the release of protons into the synaptic cleft, which transiently blocks a subset of Ca2+ channels. Keywords: Ca2+ channels, pH buffering, protons, inner hair cells, ribbon synapses, exocytosis, otoferlin, auditory nerve fiberhttp://www.sciencedirect.com/science/article/pii/S2211124718318485 |
| spellingShingle | Philippe F.Y. Vincent Soyoun Cho Margot Tertrais Yohan Bouleau Henrique von Gersdorff Didier Dulon Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses Cell Reports |
| title | Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses |
| title_full | Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses |
| title_fullStr | Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses |
| title_full_unstemmed | Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses |
| title_short | Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses |
| title_sort | clustered ca2 channels are blocked by synaptic vesicle proton release at mammalian auditory ribbon synapses |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718318485 |
| work_keys_str_mv | AT philippefyvincent clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses AT soyouncho clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses AT margottertrais clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses AT yohanbouleau clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses AT henriquevongersdorff clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses AT didierdulon clusteredca2channelsareblockedbysynapticvesicleprotonreleaseatmammalianauditoryribbonsynapses |