Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces tra...

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Autores principales:	González Inchauspe, Carlota María Fabiola, Di Guilmi, Mariano Nicolas, Uchitel, Osvaldo Daniel
Publicado:	2017
Materias:	ASIC-1a Calyx of held Glutamatergic EPSCs Protons Short-term depression Synaptic plasticity acid sensing ion channel amiloride AMPA receptor antiporter creatine phosphate glutamate receptor glutamic acid postsynaptic receptor Accn2 protein, mouse proton acidification action potential animal experiment Article cell membrane permeability depolarization depression desensitization drug mechanism electrophysiology evoked response female fluorescence glutamatergic synapse male mouse nerve cell plasticity nerve ending neurotransmitter release nonhuman patch clamp technique priority journal synapse synaptic transmission animal auditory evoked potential C57BL mouse channel gating chemistry cochlear nucleus metabolism pH physiology Acid Sensing Ion Channels Animals Cochlear Nucleus Evoked Potentials, Auditory Female Hydrogen-Ion Concentration Ion Channel Gating Male Mice Mice, Inbred C57BL Neuronal Plasticity Synapses Synaptic Transmission
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v37_n10_p2589_GonzalezInchauspe http://hdl.handle.net/20.500.12110/paper_02706474_v37_n10_p2589_GonzalezInchauspe
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_02706474_v37_n10_p2589_GonzalezInchauspe
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spelling	paper:paper_02706474_v37_n10_p2589_GonzalezInchauspe2023-06-08T15:24:53Z Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse González Inchauspe, Carlota María Fabiola Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel ASIC-1a Calyx of held Glutamatergic EPSCs Protons Short-term depression Synaptic plasticity acid sensing ion channel amiloride AMPA receptor antiporter creatine phosphate glutamate receptor glutamic acid postsynaptic receptor Accn2 protein, mouse acid sensing ion channel proton acidification action potential animal experiment Article cell membrane permeability depolarization depression desensitization drug mechanism electrophysiology evoked response female fluorescence glutamatergic synapse male mouse nerve cell plasticity nerve ending neurotransmitter release nonhuman patch clamp technique priority journal synapse synaptic transmission animal auditory evoked potential C57BL mouse channel gating chemistry cochlear nucleus metabolism pH physiology synapse synaptic transmission Acid Sensing Ion Channels Animals Cochlear Nucleus Evoked Potentials, Auditory Female Hydrogen-Ion Concentration Ion Channel Gating Male Mice Mice, Inbred C57BL Neuronal Plasticity Protons Synapses Synaptic Transmission Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward ASIC currents (IASICs) in postsynaptic MNTB neurons from wild-type mice. The inhibition of IASICs by psalmotoxin-1 (PcTx1) and the absence of these currents in knock-out mice for ASIC-1a subunit (ASIC1a-/-) suggest that homomeric ASIC-1as are mediating these currents in MNTB neurons. Furthermore, we detect ASIC1a-dependent currents during synaptic transmission, suggesting an acidification of the synaptic cleft due to the corelease of neurotransmitter and H+ from synaptic vesicles. These currents are capable of eliciting action potentials in the absence of glutamatergic currents. A significant characteristic of these homomeric ASIC-1as is their permeability to Ca2+. Activation of ASIC-1a in MNTB neurons by exogenous H+ induces an increase in intracellular Ca2+. Furthermore, the activation of postsynaptic ASIC-1as during high-frequency stimulation (HFS) of the presynaptic nerve terminal leads to a PcTx1-sensitive increase in intracellular Ca2+ in MNTB neurons, which is independent of glutamate receptors and is absent in neurons from ASIC1a-/-mice. During HFS, the lack of functional ASICs in synaptic transmission results in an enhanced short-term depression of glutamatergic EPSCs. These results strongly support the hypothesis of protons as neurotransmitters and demonstrate that presynaptic released protons modulate synaptic transmission by activating ASIC-1as at the calyx of Held-MNTB synapse. © 2017 the authors. Fil:González-Inchauspe, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Di Guilmi, M.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v37_n10_p2589_GonzalezInchauspe http://hdl.handle.net/20.500.12110/paper_02706474_v37_n10_p2589_GonzalezInchauspe
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	ASIC-1a Calyx of held Glutamatergic EPSCs Protons Short-term depression Synaptic plasticity acid sensing ion channel amiloride AMPA receptor antiporter creatine phosphate glutamate receptor glutamic acid postsynaptic receptor Accn2 protein, mouse acid sensing ion channel proton acidification action potential animal experiment Article cell membrane permeability depolarization depression desensitization drug mechanism electrophysiology evoked response female fluorescence glutamatergic synapse male mouse nerve cell plasticity nerve ending neurotransmitter release nonhuman patch clamp technique priority journal synapse synaptic transmission animal auditory evoked potential C57BL mouse channel gating chemistry cochlear nucleus metabolism pH physiology synapse synaptic transmission Acid Sensing Ion Channels Animals Cochlear Nucleus Evoked Potentials, Auditory Female Hydrogen-Ion Concentration Ion Channel Gating Male Mice Mice, Inbred C57BL Neuronal Plasticity Protons Synapses Synaptic Transmission
spellingShingle	ASIC-1a Calyx of held Glutamatergic EPSCs Protons Short-term depression Synaptic plasticity acid sensing ion channel amiloride AMPA receptor antiporter creatine phosphate glutamate receptor glutamic acid postsynaptic receptor Accn2 protein, mouse acid sensing ion channel proton acidification action potential animal experiment Article cell membrane permeability depolarization depression desensitization drug mechanism electrophysiology evoked response female fluorescence glutamatergic synapse male mouse nerve cell plasticity nerve ending neurotransmitter release nonhuman patch clamp technique priority journal synapse synaptic transmission animal auditory evoked potential C57BL mouse channel gating chemistry cochlear nucleus metabolism pH physiology synapse synaptic transmission Acid Sensing Ion Channels Animals Cochlear Nucleus Evoked Potentials, Auditory Female Hydrogen-Ion Concentration Ion Channel Gating Male Mice Mice, Inbred C57BL Neuronal Plasticity Protons Synapses Synaptic Transmission González Inchauspe, Carlota María Fabiola Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
topic_facet	ASIC-1a Calyx of held Glutamatergic EPSCs Protons Short-term depression Synaptic plasticity acid sensing ion channel amiloride AMPA receptor antiporter creatine phosphate glutamate receptor glutamic acid postsynaptic receptor Accn2 protein, mouse acid sensing ion channel proton acidification action potential animal experiment Article cell membrane permeability depolarization depression desensitization drug mechanism electrophysiology evoked response female fluorescence glutamatergic synapse male mouse nerve cell plasticity nerve ending neurotransmitter release nonhuman patch clamp technique priority journal synapse synaptic transmission animal auditory evoked potential C57BL mouse channel gating chemistry cochlear nucleus metabolism pH physiology synapse synaptic transmission Acid Sensing Ion Channels Animals Cochlear Nucleus Evoked Potentials, Auditory Female Hydrogen-Ion Concentration Ion Channel Gating Male Mice Mice, Inbred C57BL Neuronal Plasticity Protons Synapses Synaptic Transmission
description	Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward ASIC currents (IASICs) in postsynaptic MNTB neurons from wild-type mice. The inhibition of IASICs by psalmotoxin-1 (PcTx1) and the absence of these currents in knock-out mice for ASIC-1a subunit (ASIC1a-/-) suggest that homomeric ASIC-1as are mediating these currents in MNTB neurons. Furthermore, we detect ASIC1a-dependent currents during synaptic transmission, suggesting an acidification of the synaptic cleft due to the corelease of neurotransmitter and H+ from synaptic vesicles. These currents are capable of eliciting action potentials in the absence of glutamatergic currents. A significant characteristic of these homomeric ASIC-1as is their permeability to Ca2+. Activation of ASIC-1a in MNTB neurons by exogenous H+ induces an increase in intracellular Ca2+. Furthermore, the activation of postsynaptic ASIC-1as during high-frequency stimulation (HFS) of the presynaptic nerve terminal leads to a PcTx1-sensitive increase in intracellular Ca2+ in MNTB neurons, which is independent of glutamate receptors and is absent in neurons from ASIC1a-/-mice. During HFS, the lack of functional ASICs in synaptic transmission results in an enhanced short-term depression of glutamatergic EPSCs. These results strongly support the hypothesis of protons as neurotransmitters and demonstrate that presynaptic released protons modulate synaptic transmission by activating ASIC-1as at the calyx of Held-MNTB synapse. © 2017 the authors.
author	González Inchauspe, Carlota María Fabiola Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel
author_facet	González Inchauspe, Carlota María Fabiola Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel
author_sort	González Inchauspe, Carlota María Fabiola
title	Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
title_short	Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
title_full	Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
title_fullStr	Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
title_full_unstemmed	Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
title_sort	activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v37_n10_p2589_GonzalezInchauspe http://hdl.handle.net/20.500.12110/paper_02706474_v37_n10_p2589_GonzalezInchauspe
work_keys_str_mv	AT gonzalezinchauspecarlotamariafabiola activatedbyevokedreleasedprotonsmodulatesynaptictransmissionatthemousecalyxofheldsynapse AT diguilmimarianonicolas activatedbyevokedreleasedprotonsmodulatesynaptictransmissionatthemousecalyxofheldsynapse AT uchitelosvaldodaniel activatedbyevokedreleasedprotonsmodulatesynaptictransmissionatthemousecalyxofheldsynapse
_version_	1768541750149775360

Activated by evoked released protons modulate synaptic transmission at the mouse calyx of held synapse

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